Approach
Management of bradycardia depends on multiple factors, such as the acuity and severity at presentation, the nature and reversibility of precipitating events, and underlying electrophysiological and cardiac abnormalities. It is important to identify whether patients have symptoms attributable to bradycardia by taking a careful history, especially when incidentally detected on heart rhythm monitoring either at home or in hospital. Patients presenting with haemodynamic compromise, signs of cerebral hypoperfusion, progressive heart failure, or life-threatening arrhythmias secondary to bradycardia require urgent treatment, including the use of temporary pacing.
The most common reversible causes of bradycardia include drug-induced bradycardia related to drugs such as beta-blockers, calcium-channel blockers, and anti-arrhythmic drugs; increased vagal tone; and electrolyte abnormalities. A detailed review of the patient's home medications is important, especially for patients with hypertension, coronary artery disease, congestive heart failure, atrial and ventricular arrhythmias, seizure disorders, and psychiatric illnesses. In patients on multiple medications at home, a check for drug-drug interactions that may lead to drug toxicity should be performed. A significant number of these patients may have resolution of bradycardia after adjustment and/or discontinuation of offending medications, and may not require permanent pacemaker implantation. On the other hand, patients who need to be on rate-lowering medications (e.g., beta-blockers in patients with coronary artery disease) may need permanent pacemaker implantation in order to stay on these medications.
The role of medicines to treat bradycardia is generally limited to emergency situations. Permanent pacing is the principal therapeutic modality for the management of persistent bradycardia.
Haemodynamically unstable patients
Bradycardia associated with haemodynamic compromise (i.e., systemic hypotension, signs of cerebral hypoperfusion, progressive heart failure, or angina) or life-threatening ventricular tachyarrhythmia represents a true medical emergency. Medical therapy should be started immediately, regardless of the cause, and continued until temporary cardiac pacing is initiated.
The most common medications used to increase ventricular rate are intravenous atropine and epinephrine (adrenaline). Dobutamine can also be considered, especially when there is evidence of concomitant systolic heart failure. Some clinicians use isoprenaline, as it is the strongest beta agonist. However, isoprenaline may perpetuate hypotension, if present, due to its vasodilatory effects, and so is not generally recommended. Epinephrine (adrenaline), on the other hand, due to its combined alpha and beta agonist properties, may help increase blood pressure as well as heart rate. In post-cardiac transplant patients without evidence of autonomic re-innervation, atropine should not be used due to the risk of paradoxical complete heart block. For post-cardiac transplant patients and patients with acute spinal cord injury, aminophylline or theophylline are reasonable choices to treat bradycardia.[11] Where an underlying cause can be identified (e.g., prescription drug toxicity), this should be addressed.
Patients who are not responsive to medical therapy require prompt temporary pacing. The two most commonly used modes of temporary pacing are transcutaneous and transvenous.
Transcutaneous pacing can be applied rapidly through external adhesive electrodes. However, this pacing modality usually serves as a bridge to transvenous pacing because it causes painful skeletal muscle stimulation and usually requires sedation. Furthermore, the efficacy of transcutaneous pacing to provide stable ventricular capture is limited to 78% to 94%.[54][55] It can be used as a sole temporary pacing modality to provide back-up in some patients with transient, infrequent, and short-lived episodes of bradycardia until a reversible cause is corrected or a permanent pacemaker is implanted.
Transvenous pacing is the most secure and effective modality for patients who require continuous temporary pacing. The temporary pacing lead is usually placed in the right ventricle or, rarely, in the right atrium or both chambers using a central vein (femoral, subclavian, or internal jugular). A mechanical prosthetic tricuspid valve is a contraindication to right ventricular pacing. Complications are common (up to 20%) and related most commonly to venous access, infection, thromboembolism, heart perforation, or lead dislodgement. Ideally, pacing should not exceed more than a few days because of the incremental risk of infection.[54][55]
Haemodynamically stable patients: general approach
These patients are treated according to the underlying cause and usually require either temporary or permanent pacing, depending on whether sinus node dysfunction or atrioventricular (AV) conduction disturbance is present. Permanent pacing is the only available therapeutic modality for persistent bradycardia problems owing to non-reversible causes.
When permanent pacing is being considered, it is essential to establish a clear association between bradycardia and symptoms attributable to bradycardia, since many ambulatory patients may have asymptomatic bradycardia and do not necessarily need permanent pacemaker implantation. Testing for underlying structural heart disease, especially evaluation of left ventricular systolic function, is essential before making a decision regarding the type of device (pacemaker versus implantable cardioverter defibrillator [ICD]) to be implanted. Whenever possible, attempts should be made to use atrial pacing and native atrio-ventricular conduction in order to reduce the burden of right ventricular pacing, especially in patients with normal ventricular systolic function. Chronic right ventricular pacing can cause or worsen ventricular dyssynchrony, which can cause deterioration in left ventricular systolic function. Single-chamber pacing (either using a conventional right ventricular pacing lead or using a leadless pacemaker) should only be considered in patients in whom the anticipated pacing burden is low.
Pacing modes are described by a 5-letter code.
The first letter designates the chamber that is paced (O is none; A is atrium; V is ventricle; D is dual chamber).
The second letter is the chamber in which sensing occurs (O is none; A is atrium; V is ventricle; D is dual chamber).
The third letter is the response to sensed event (O is none; I is inhibition; T is triggered; D is both inhibition and triggering).
The fourth letter usually refers to the rate response (R).
The fifth letter refers to anti-tachycardia capabilities and is not used commonly.
All modern pacemakers are multi-programmable. The choice of the specific pacemaker mode is usually dictated by the underlying electrophysiological abnormality.
Shared decision-making should be undertaken whenever an intracardiac device (pacemaker or ICD) is being considered as a treatment option. This involves a detailed conversation between the patient and the various healthcare providers about the potential benefits, risks, complications (both short-term and long-term), and alternative treatment options (if available) pertaining to device implantation. This conversation should be individualised to the patient's clinical condition, and should incorporate the patient's own beliefs, values, goals, and expectations of the clinical care being provided. In addition, information regarding ambulatory device monitoring, need for arm movement restrictions for a few weeks post-implant, avoidance of certain activities (e.g., using high-energy arc welding equipment) in pacemaker-dependent patients, and future need for generator changes and possible lead revisions or device upgrades, should be provided.
Haemodynamically stable: sinus node dysfunction
Asymptomatic or mild symptoms
In patients with sinus node dysfunction owing to a reversible or isolated cause (e.g., specific medicine, electrolyte disorder, or vasovagal event, such as taking blood), the underlying cause should be addressed (e.g., stopping responsible drug, correction of electrolyte abnormality, regulation of thyroid dysfunction). Theophylline may be used in selected patients with mild symptoms, such as predominantly exertional dizziness and/or fatigue.[56][57]
In patients with sinus node dysfunction owing to a non-reversible cause and no symptoms or minimal symptoms, no specific treatment is required.[11][41]
Severe symptoms
Acute treatment is needed if there are severe symptoms or sequelae, including syncope, near-syncope, hypotension, marked fatigue, or ventricular arrhythmias (including torsades de pointes). In patients with a non-reversible cause, the role of pharmacotherapy is limited and permanent pacing is the treatment of choice. In patients with a reversible cause, temporary pacing is needed and underlying causes should be corrected.
Atrial-based (AAI), ventricle-based (VVI), and dual chamber (DDD) pacing modes are all useful in correcting bradycardia caused by sinus node dysfunction, although the optimal pacing mode remains controversial. Nonetheless, growing evidence indicates that AAI, which avoids pacing of the ventricle, is associated with a relatively lower risk of atrial fibrillation and heart failure.[58] Because patients with sinus node disease are at risk of the development of AV block or atrial fibrillation, DDD pacemakers incorporating algorithms that enable the minimisation of right ventricular pacing (functional AAI pacing) are preferred over the single-lead AAI system.[59][60]
Concomitant impaired systolic left ventricular (LV) function
Patients need to be evaluated for possible ICD placement. This can be accomplished by imaging (echocardiography, or less commonly, cardiac computed tomography or cardiac magnetic resonance imaging) to assess left ventricular systolic function. If new left ventricular systolic dysfunction is identified during evaluation of a patient with bradycardia, exclusion of underlying structural heart disease and coronary artery disease should be done prior to permanent device implantation.
Accumulating evidence suggests that right ventricular pacing in patients with systolic LV dysfunction may be associated with an increased risk of atrial fibrillation, worsening heart failure, and mortality secondary to LV desynchronisation. Therefore, pacing of the ventricle should be avoided in patients who do not need it.[58][61] Dual-chamber pacemakers incorporating algorithms that enable the minimisation of ventricular pacing (functional AAI pacing) are preferred in these patients.[62]
Haemodynamically stable: acquired AV block
Asymptomatic patients
Permanent pacing is indicated only when any of the following are present: high-grade AV block, Mobitz type II second-degree AV block, third-degree AV block, or evidence of infranodal block that is not caused by a physiological mechanism or reversible cause, regardless of symptoms. In addition, patients who underwent catheter ablation of the AV junction; or those who develop persistent AV block after surgical or transcutaneous implantation of aortic or mitral valve prostheses, or after surgical myectomy or alcohol septal ablation for hypertrophic cardiomyopathy; and those with certain specific neuromuscular diseases (e.g., myotonic dystrophy type 1 or Kearns-Sayre syndrome) and infiltrative cardiomyopathies (sarcoidosis, amyloidosis) with any of the above AV conduction abnormalities, should undergo permanent pacemaker implantation.[11][41]
Symptomatic patients
In addition to symptomatic patients who fall into one of the above categories, patients with persistent atrial fibrillation and symptomatic bradycardia, and patients with symptomatic bradycardia who need to be on rate-lowering medications for long-term guideline-directed management of another cardiac condition (e.g., coronary artery disease, systolic congestive heart failure), should be referred for permanent pacemaker implantation.[11]
VVI, DDD, or atrial synchronous-ventricular inhibited (VDD) pacing modes are useful in correcting bradycardia caused by AV block. Although the optimal pacing mode remains controversial, modes that preserve AV synchrony (VDD or DDD) are preferred.
Among patients who have a clear indication for permanent pacemaker implantation, moderate to severe left ventricular systolic dysfunction (estimated left ventricular ejection fraction between 36% and 50%), and a high (>40%) expected burden of ventricular pacing, one should consider the use of cardiac resynchronisation therapy or biventricular pacemaker implantation, or consider implantation of a conduction system pacemaker.[11]
Patients with symptomatic bradycardia in whom the level of AV block is at the level of the AV node (supra-Hisian AV block) should be considered for a His-bundle lead-based dual chamber pacemaker instead of a conventional right ventricular lead-based dual chamber pacemaker, to reduce the long-term deleterious effects of chronic right ventricular pacing.
Reversible cause
Underlying cause should be addressed (e.g., ceasing drug treatment, administration of electrolytes, or correction of thyroid dysfunction).[11][41]
Temporary pacing should be considered when any of the following is present: high-grade AV block, Mobitz type II second-degree AV block, third-degree AV block, or evidence of infranodal block, regardless of symptoms. After correction of reversible causes, re-assessment of AV conduction should be performed before a clinical decision about permanent pacemaker implantation is made.
Non-reversible cause
Permanent pacing is the only available therapeutic modality for persistent acquired AV block that is a result of non-reversible causes.
As a general rule, all symptomatic patients with AV block require permanent pacing regardless of the specific type or anatomical level of AV block.
VVI, DDD, and VDD pacing modes are useful in correcting bradycardia caused by AV block. Although the optimal pacing mode remains controversial, modes that preserve AV synchrony (VDD or DDD) are preferred.
Concomitant impaired systolic left ventricular function
Patients need to be evaluated for possible ICD placement.
Accumulating evidence suggests that right ventricular pacing in patients with systolic left ventricular dysfunction may be associated with an increased risk of atrial fibrillation, worsening heart failure, and mortality secondary to LV desynchronisation. Therefore, pacing of the ventricle should be avoided in patients with preserved AV conduction.[58][61] Cardiac resynchronisation therapy (biventricular pacing) was superior to right ventricular pacing in reducing a composite of all-cause mortality, heart failure hospitalisation, and left ventricular end systolic volume in patients with left ventricular ejection fraction <50%; New York Heart Association (NYHA) class I, II, or III; and >40% right ventricular pacing (e.g., patients with AV block).[63] Whether the same results apply to patients with bradycardia and normal ejection fraction requiring >40% right ventricular pacing remains unclear.
Haemodynamically stable: congenital complete AV block
Treatment approach to patients with congenital complete AV block continues to evolve. There is a general consensus that permanent pacing is indicated for all symptomatic patients or for asymptomatic patients with any of the following: wide QRS escape rhythm, complex ventricular arrhythmia, a mean daytime heart rate of less than 50 bpm, or impaired systolic left ventricular function. In addition, patients with adult congenital heart disease (ACHD) who have significant AV conduction abnormalities (high-grade AV block, Mobitz II second-degree AV block, or third-degree AV block that is not expected to resolve) should undergo permanent pacemaker implantation, and pacemaker algorithms that reduce the risk of atrial arrhythmias should be incorporated in these devices.[11] Although not agreed universally, pacing should be considered strongly in asymptomatic patients with ventricular escape rhythm of below 50 bpm or prolonged ventricular pauses. Some data suggest that early institution of pacing in asymptomatic patients may improve survival. However, whether or not all asymptomatic patients with congenital AV block require permanent pacemaker implantation remains controversial. Pacing modes that preserve AV synchrony (VDD or DDD) are usually used.
Concomitant impaired systolic left ventricular function
Patients need to be evaluated for possible ICD placement.
Accumulating evidence suggests that right ventricular pacing in patients with systolic left ventricular dysfunction may be associated with increased risk of atrial fibrillation, worsening heart failure, and mortality secondary to left ventricular desynchronisation. Therefore, pacing of the ventricle should be avoided in patients with preserved AV conduction.[58][61]
Cardiac resynchronisation therapy (biventricular pacing) was superior to right ventricular pacing in reducing a composite of all-cause mortality, heart failure hospitalisation, and left ventricular end systolic volume in patients with left ventricular ejection fraction <50%; NYHA class I, II, or III; and >40% right ventricular pacing (e.g., patients with AV block).[63] Current guidelines recommend that either biventricular pacing or conduction system pacing should be preferred over right ventricular pacing for patients with a left ventricular ejection fraction between 36% and 50% and AV block, who have an indication for permanent pacing and are expected to require ventricular pacing >40% of the time to reduce the risk of developing systolic heart failure.[11] Whether the same results apply to patients with bradycardia and normal ejection fraction requiring >40% right ventricular pacing remains unclear.
Haemodynamically stable: vagally mediated bradycardia
Bradycardia mediated by increased vagal activation and peripheral vasodilation secondary to reduced sympathetic activity are integral parts of the neurocardiogenic response manifested by systemic hypotension. In this clinical situation, treating bradycardia in itself may be ineffective in alleviating symptoms in many patients with neurocardiogenic events. Understanding the relative contribution of the mechanisms in each individual case is critical in defining the therapeutic approach.
Carotid sinus hypersensitivity syndrome
Pacing may be indicated for patients with recurrent symptoms who demonstrate a hyperactive response to carotid sinus massage (defined as ventricular asystolic pause of over 3 seconds), are thought to have symptoms owing to hypersensitive carotid sinus, and have no other explainable cause for syncope.
Patients without these indications do not require treatment.
Neurocardiogenic or vasovagal syncope
The initial approach is usually based on education and lifestyle modification regardless of the intrinsic autonomic mechanism underlying syncopal events. The main aspects of this approach include:
Identification and avoidance of precipitating factors
Measures to be taken during impending events, such as lying down, elevation of legs, and tensing manoeuvres
Adequate fluid and salt intake.
Data documenting specific therapy for vasovagal syncope are sparse. Multiple drugs with different mechanisms have been used with no or little documented benefit.[64][65] Isolated studies demonstrating benefit of medical therapies, including fluoxetine, have been published.[66] European guidelines state that fludrocortisone should be considered in young patients with orthostatic vasovagal syncope with low-to-normal arterial blood pressure, while midodrine should be considered in patients with vasovagal syncope and orthostatic symptoms. Beta-blocking agents are not generally indicated for the management of neurocardiogenic syncope.[67]
Use of permanent pacing should be reserved for patients with recurrent severe episodes of syncope refractory to medical therapy who have significant asystolic episodes documented during clinical events. In such patients, dual-chamber permanent pacing with rate-drop response or closed loop stimulation should be the preferred pacing mode.[68][69]
Heart-rate response observed during tilt-table testing may not correlate with that during clinical events and should be used with caution for the selection of patients who may or may not benefit from pacing.
When pacing is considered for neurocardiogenic syncope, the DDD pacing mode is considered to be the preferred pacing mode. The value of programmable pacemaker features such as rate-drop response (during which the rate increases abruptly if a gradual slowing is seen), or closed loop stimulation (during which pacing rate increases if there is evidence of changes in local impedance that may reflect changes in right ventricular contractility by a proprietary algorithm), may be beneficial.[64][65]
Haemodynamically stable: bradycardia associated with neurological disorders
Bradycardia in patients with neurological disorders can be acute (e.g., Cushing's reflex associated with increased intracranial pressure) or chronic. In many situations, the bradycardia may be transient, and clinical monitoring of the bradycardia may be preferable. However, after elimination of reversible causes of bradycardia in these patients, permanent pacing may be needed in a small proportion of patients with neurological disorders.
In patients with epilepsy associated with severe symptomatic bradycardia (ictal bradycardia) that is not controlled with anticonvulsants, permanent pacing is a reasonable treatment option for reducing the severity of symptoms.[11]
Patients diagnosed with myotonic dystrophy type 1 or Kearns-Sayre syndrome, who have evidence of second-degree atrioventricular block, third-degree atrioventricular block, or an abnormal electrophysiology study (H-V interval of greater than or equal to 70 ms), should be referred for pacemaker (or ICD if there is concomitant systolic dysfunction) implantation regardless of symptoms, if meaningful survival of more than 1 year is expected.[11][41]
Patients with traumatic spinal cord injury (above the sixth thoracic vertebra level) can have episodes of profound bradycardia in response to painful or noxious stimuli, due to impaired sympathetic innervation and autonomic dysreflexia. These episodes usually resolve over time and with elimination of noxious stimuli, and conservative measures and watchful waiting for resolution of symptomatic bradycardia is preferable.[11]
Special considerations for frail patients
According to an expert consensus document, the prevalence of bradycardia and bradyarrhythmias increases with advanced age and the presence of comorbid conditions. Increased frailty may be associated with reduced sinoatrial node function, slowing of electrical conduction, which may manifest in the form of reduced heart rate, blunted heart rate response to exercise, as well as worsening AV and intraventricular conduction.[70]
Frail patients may have reduced capacity for metabolising cardiovascular medicines including rate lowering medicines and anti-arrhythmic medicines, unpredictable pharmacokinetics, and worsening hepatic and/or renal function-making them more vulnerable to drug-induced adverse effects and dose-limiting bradycardia.[70]
Frail patients on multiple medicines may also have drug-drug interactions which may further impact the choice and dose of cardiovascular medicines. Caution must be exercised in prescribing rate lowering and anti-arrhythmic medicines in frail patients. Particular care should be taken to review the patient's comorbid conditions and previously prescribed medicines before starting cardiac medicines in frail patients.[70]
Closer monitoring of renal function, as well as hepatic and endocrine function if relevant, is recommended in frail patients, and dosages adjusted accordingly. Certain medicines such as digoxin should be avoided in the elderly and frail patients due to concern for development of digoxin toxicity, even at lower serum levels.[70]
Existing guidelines recommend consideration of patient frailty when deciding between cardiac resynchronisation therapy (CRT)-pacemaker over CRT-defibrillator implantation, and also stressed the need for a comprehensive review of the patient's clinical condition and risk/benefit ratio of cardiac device implantation in elderly and/or frail patients.[70]
Procedural complications from pacemaker implantation such as pneumothorax, lead dislodgment, and device erosion due to low body weight are more common in the frail and elderly patients.[70]
Frail patients with high-grade AV block or infrequent pauses due to sinus node dysfunction or intermittent high-grade AV block should be considered for single-chamber pacemaker implantation rather than dual-chamber pacing, using either a transvenous single-lead right ventricular pacemaker or a transcutaneous leadless pacemaker.[70] For more detailed information, see Frailty.
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