Bradycardia
Bradycardia is defined as a resting heart rate below 60 beats per minute (b.p.m.). A slow heart rate can occur naturally under various circumstances and is not necessarily associated with a medical condition. For example, some highly trained athletes have bradycardia. However, there is also pathological bradycardia, which is caused by conditions that affect the electrical conduction system of the heart, including sick sinus syndrome (SSS) and/or atrioventricular (AV) block.1 Bradycardia does not necessarily require treatment unless it causes symptoms. People suffering from symptomatic bradycardia can present with dizziness, confusion, palpitations, breathlessness, exercise intolerance and syncope (blackout or fainting). However, bradycardia, and symptoms related to it, may be intermittent or may be non-specific, particularly in the elderly.
Sick sinus syndrome
Sick sinus syndrome is caused by dysfunction of the sinus node, the heart’s natural pacemaker. The sinus node consists of a cluster of cells that is situated in the upper part of the right atrium (the right upper chamber of the heart). The sinus node generates the electrical impulses that are conducted through the heart and stimulate it to contract. SSS covers a spectrum of arrhythmias with different underlying mechanisms, manifested as bradycardia, tachycardia (fast heart rate) or a mix of the two, but also as chronotropic incompetence (the inability of the heart to increase its rate appropriately with increased activity, leading to exercise intolerance). SSS manifesting as bradyarrhythmias includes sinus bradycardia, sinus arrest, sinoatrial (SA) exit block and alternating bradyarrhythmias and tachyarrhythmias such as bradycardia–tachycardia syndrome (BTS).1,2
In sinus arrest or sinus pause, the sinus node transiently ceases to generate electrical impulses.3 The pause can last from a couple of seconds to several minutes. The sinus pause usually allows escape beats or rhythms to occur, when other pacemakers in the heart initiate contraction of the ventricles. In SA exit block, the sinus node depolarises normally, but the signal is blocked before it leaves the sinus node, leading to intermittent delay (first-degree SA block) or failure (second-degree SA block) of atrial depolarisation.
Atrioventricular block
Atrioventricular block can occur independently from SSS, and so patients suffering from symptomatic bradycardia due to SSS may also have or develop AV block. In AV block, the electrical impulses from the sinus node in the right atrium to the ventricular chambers are slowed or blocked at the AV node or within the His–Purkinje system, which conducts electrical impulses between the atria and ventricular chambers. Although heart block can be present at birth (congenital), people are more likely to develop the condition, with the risk increasing with age along with the incidence of heart disease. As in SA block, there are several degrees of AV block.4 First-degree AV block is usually asymptomatic and occurs when the electrical impulses slow as they pass through the AV node, but all impulses reach the ventricles. In second-degree AV block, some of the electrical impulses from the sinus node are unable to reach the ventricles, a condition that is more likely to present with symptoms such as syncope. In third-degree AV block (complete heart block), there are no electrical impulses between the atrial and ventricular chambers. In the absence of any electrical impulses from the atria, the ventricles produce escape beats, which are usually slow.
Aetiology and pathology
The resting heart rate in healthy people does not change with increasing age;5 however, bradycardia due to SSS becomes more common in older people because of idiopathic degeneration or development of scarring of the sinus node, both of which occur with ageing.2 However, SSS can also be caused by extrinsic factors that can mimic or exacerbate SSS, such as some types of medication (e.g. calcium channel blockers and beta-blockers), electrolyte disturbances, hypothyroidism, hypothermia and toxins. SSS has also been linked with diseases and conditions that cause scarring or damage to the heart’s electrical system, such as atrial fibrillation (AF) and heart failure (HF).1,2
Atrioventricular block can also be either congenital or acquired. Acquired AV block is associated with coronary heart disease, myocardial infarction, cardiomyopathy, heart surgery and with the use of many antiarrhythmic agents.
Incidence and prevalence
Sick sinus syndrome usually occurs in older adults, but it can affect persons of all ages, and it affects men and women equally.2 The incidence of AV conduction abnormalities also increases with advancing age.6 However, the prevalence of bradyarrhythmias due to SSS requiring permanent pacemaker implant is unknown,7 as is the breakdown of the prevalence of SSS with and without a concurrent AV block. Hospital Episode Statistics data from October 2012 to September 2013 included 2490 patients with a primary diagnosis of SSS in NHS hospitals in England.
Diagnosis
Diagnosis of SSS is made by considering a patient’s medical history and symptoms and through the use of electrocardiography (ECG). Diagnosis sometimes proves difficult because symptoms and electrocardiographic abnormalities are intermittent. When 12-lead ECG does not yield a diagnosis, prolonged ECG monitoring, such as Holter monitoring (ECG monitoring for 24–48 hours) or longer-duration cardiac monitoring either with event ECG recorders for weeks at a time or with an implantable loop recorder for months at a time, may help accurate diagnosis.2,8 SSS manifested as chronotropic incompetence is usually assessed through various exhaustive and symptom-limited exercise tests; however, there are no well-validated standards for diagnosing SSS in this setting.5
Atrioventricular conduction is also assessed by ECG. Adequate AV conduction, that is, absence of AV block, has been defined as presence of 1 : 1 conduction at rates of 140 b.p.m.9
Prognosis and impact of health problem
The prognosis of bradycardia due to SSS depends on the aetiology. If the underlying cause is, for example, medication, hypothyroidism or electrolyte imbalance, then the bradycardia may resolve if the triggering cause is treated or removed. However, for most people, SSS is idiopathic and progressive, with a highly variable development of the disease. People with asymptomatic SSS do not require therapy. The only effective treatment for patients suffering from symptoms is implantation of a permanent pacemaker.2 However, pacemaker implantation does not cure or affect the prognosis of SSS, and pacemakers are implanted with the aim of alleviating symptoms and improving the patient’s quality of life (QoL). Pacemaker implantation is associated with considerable risk for the patient, and therefore careful consideration must be given to the balance between potential benefits and adverse effects of treatment. Although pacemaker implantation has been shown to improve QoL for patients with bradycardia and sinus node dysfunction,10,11 it has been noted that women and older adults may achieve lower levels of improvement in QoL than other groups.12 Additionally, research suggests that there may be differences between the sexes at pacemaker implantation, with less favourable outcomes for women in terms of complications.13
Patients with SSS are at risk of developing a complete AV block, with considerable variation in the estimates of risk of AV block (from < 1% up to 4.5% per year).4,14 A patient with SSS who develops AV block will require ventricular pacing (VP) and, consequently, an upgrade to a dual-chamber pacemaker if they already have a single-chamber atrial pacemaker. People with SSS may also develop BTS with AF as the tachyarrhythmia, which in turn leads to an increased risk of stroke.2
Measurements of disease
Symptomatic bradycardia, and implantation of permanent pacemakers to relieve the symptoms, can have a significant impact on a patient’s QoL.4 QoL has been measured using many different generic and disease/treatment-specific measures in pacemaker trials. Recommended generic measures include the Short Form Questionnaire-36 items (SF-36), a health questionnaire with 36 questions, which looks at functional health, general well-being and physical and mental health.15
The Karolinska Questionnaire,16 which has been validated in patients paced for bradyarrhythmia, contains 16 questions on cardiovascular symptoms relevant to pacemaker patients. The Specific Activity Scale (SAS)17 is another disease-specific questionnaire for the functional classification of patients with cardiovascular disease (CVD). Based on physical capacity, patients are divided into class I (unlimited exercise capacity) to class IV (very low exercise tolerance). Many pacemaker trials also use the New York Heart Association (NYHA) functional scale, which is used to classify patients’ cardiac disease according to the severity of their symptoms. Similar to the SAS, patients can fall into four categories based on the limitations on physical activity, from class I (no limitation of physical activity) to class IV (symptoms of HF at rest and inability to carry out any physical activity without discomfort).
Current service provision
Current guidelines
The National Institute for Health and Care Excellence (NICE)’s technology appraisal (TA) number 88,18 which was published in 2005, recommends dual-chamber pacemakers for patients with symptomatic bradycardia that is due to SSS, AV block or a combination of the two.18 However, in a few exceptional cases single-chamber atrial or ventricular pacemakers are preferred:
single-chamber atrial pacemakers for patients with SSS in whom, after full evaluation, there is no evidence of impaired AV conduction
single-chamber ventricular pacemakers for patients with AV block with continuous AF
single-chamber ventricular pacemakers for patients with AV block alone, or in combination with SSS, when patient-specific factors, such as frailty or the presence of comorbidities, influence the balance of risks and benefits in favour of single-chamber VP.
Similarly, guidelines from the American College of Cardiology (ACC) and American Heart Association (AHA), published in 2008, recommend dual-chamber pacemakers for AV block and for SSS if there is a suspected abnormality of AV conduction or increased risk of future AV block.4 Single-chamber ventricular pacemakers are recommended for patients with AV block and chronic AF or other atrial tachyarrhythmias, and single-chamber atrial pacemakers are recommended for patients with SSS with no suspected abnormality of AV conduction and who are not considered to be at increased risk of future AV block.
In 2013, the European Society of Cardiology (ESC) published its guidelines on cardiac pacing and cardiac resynchronisation therapy.7 ESC recommends dual-chamber pacemakers as a first choice for patients with SSS and/or AV block, with the exception of patients with a persistent AV block and continuous AF, for whom a single-chamber ventricular pacemaker is recommended.
The differences in recommendations between the more recent ESC guidelines and those of NICE and the ACC/AHA are linked to the completion and publication of the DANPACE trial,19 which has provided new evidence on the comparison of single-chamber atrial pacing with dual-chamber pacing in SSS with no evidence of AV block. The objectives for this multiple technology appraisal (MTA) were to evaluate formally the data from DANPACE1 study and to identify any other evidence in this area.
Current pacemaker usage in the NHS
During 2012–13 in England, more than 20,000 people had a single- or a dual-chamber pacemaker implanted and just over 8000 people had an implanted pacemaker renewed.20 The median length of hospital stay was 2 days for implantation of both single- and dual-chamber pacemaker systems, resulting in 82,000 bed-days in the UK in 2012–13. Of the newly implanted single and dual pacemakers, SSS was the fourth most prevalent primary diagnosis (9.5%), after AF and flutter (22.5%), complete AV block (18.8%) and second-degree AV block (10.6%).8 Among patients with a primary diagnosis of SSS (2490 patients), 67.5% had a dual-chamber pacemaker implanted, 14.8% had a single-chamber pacemaker and 2.2% had a reoperation on an existing implanted pacemaker.8
The target for the implantation rate of new pacemakers in England and Wales is 700 pacemakers per million people. In 2012, the total implant rate in England and Wales fell short of this target, reaching 559 per million of the population.21 In England, implantation rates varied between 379 and 638 new pacemaker implants per million people in different parts of the country, although a decrease in variability was noticed across the country from 2010 to 2012.21
Description of technology under assessment
Pacemakers
Pacemakers are small battery-driven devices which regulate abnormal heart rhythms. A pacemaker consists of a generator and one or more leads, which are connected to the heart. The leads will sense the heart’s electrical activity and, when it becomes too slow, an electrical impulse from the generator will initiate contraction of the heart.
Single-chamber pacemakers have one lead which is attached to either the atrium (atrial pacing) or the ventricle (VP). Dual-chamber pacemakers have two leads: one lead is attached to the atrium and the second to the ventricle.
The North American Society of Pacing and Electrophysiology (NASPE) and the British Pacing and Electrophysiology Group (BPEG) have established nomenclature to describe the different pacing modes of pacemakers, which is a four-letter combination ().22 The first letter indicates which chamber or chambers are paced, and the second letter specifies which chamber(s) are sensed. Letters I and II are usually, but not necessarily, the same. The third letter describes the mode of response to sensing. The pacemaker can be inhibited (I), if it senses a spontaneous depolarisation; triggered (T), if it senses that no depolarisation has occurred (uncommon); or both inhibited and triggered (D).
Definition of generic antibradycardia pacing codes (NASPE/BPEG)
In an AAI or VVI pacemaker, the pacemaker senses an atrial or ventricular event and withholds its signal. DDI pacemakers will inhibit the output of the device in either chamber where it senses a signal. The most common example of the letter D in the third position is in DDD pacemakers, which have dual functionality. On sensing an atrial signal, the DDD pacemaker initially inhibits the atrial output, which triggers a timer that, after a set time interval (AV delay), initiates a ventricular output. If the DDD device senses a ventricular signal during the triggering interval, the pacemaker also inhibits the ventricular output. The fourth letter specifies whether or not the pacemaker is programmed to sense and increase the heart rate in response to physical, mental or emotional activity. This is termed rate response.
Modern pacemakers have numerous programmable features that can be altered to optimise pacemaker function. Programming is a complex and rapidly evolving technical area, and a detailed description of pacemaker programming is beyond the scope of this report; thus, a few key parameters are summarised:
Rate responsiveness As mentioned previously, some pacemakers can be programmed to vary the pacing rate in response to the patient’s activity level. Rate-responsive pacemakers control heart rate by sensing body movement or breathing or by closed-loop stimulation. Closed-loop stimulation determines the appropriate heart rate based on intracardiac impedance measurements, which reflect information from the autonomic nervous system.
AV delay The AV delay is the time interval between an atrial paced or sensed event and the delivery of a VP stimulus in dual-chamber pacemakers. If intrinsic conduction is more rapid than the duration of the programmed AV delay, the intrinsic signal will inhibit VP.
Mode switching Dual-chamber pacemakers may have an additional feature called mode switching.
23 Mode-switch algorithms track tachyarrhythmias, such as AF, and when these occur trigger a non-tracking mode, or VP to avoid tachycardia. Atrial arrhythmias would otherwise cause sustained high ventricular rates. When the atrial rate falls below the rate programmed for mode switch, the pacemaker changes back to a tracking mode.
23
Implant procedure and follow-up
Pacemakers are usually implanted under local anaesthetic. An incision is made below the collarbone to facilitate lead implantation and a pocket is created under the skin to hold the pacemaker device. The pacing lead is inserted into the heart through a major vein. One end of the lead is securely lodged in the tissue of the heart and the other end is connected to the pacemaker. The position of the lead is checked using radiographic imaging. Testing and programming of the pacemaker may sometimes be done wirelessly and can be changed at any time. The hospital stay is usually brief and the implant procedure could be carried out as day surgery or might require a single overnight stay in hospital. Implantation of a dual-chamber pacemaker may take longer than implantation of a single-chamber pacemaker, because dual-chamber pacemakers require the insertion and placement of two leads. The requirement for an additional lead in dual- versus single-chamber pacemakers might result in an associated increased risk of complications, such as lead displacement.24
People with permanently implanted pacemakers require regular follow-up to check the function of the pacemaker leads, the frequency of utilisation and the battery life of the pacemaker, and for abnormal heart rhythm.25 The battery life of a pacemaker is about 5–8 years; after this time, replacement of the pacemaker will be required. Replacement of the pacemaker involves making an incision over the previous site of insertion, removing the old pacemaker generator, checking the lead(s), and, if satisfactory, attaching a new generator to the existing lead(s). Problems with pacemaker leads, such as loss of contact between the lead and the heart, require reoperation. Where repair of a fault with a lead is necessary, the old lead may be left in place but disconnected from the pacemaker and a new lead implanted. Removal of old leads can be complicated by the formation of scar tissue connecting the lead to the vein and/or the heart.
Complications
Most complications occur during or soon after implantation of a pacemaker. Some of the more common complications are lead displacement (1.4–2.1%) and puncture of the lung when placing the leads, which can lead to a pneumothorax (1.9%) or haemothorax.26,27 One of the most serious, but rarer, complications that can arise during the implant procedure is cardiac perforation. There is also the risk of infection of the pacemaker pocket or the leads.27,28 Complications occurring at a later date mainly involve dysfunction of the pacemaker or of the leads, that is, failure to pace or sense appropriately. Other late complications include infection or erosion of the pacemaker site or its leads.28
Reoperation may be required as a result of a complication, such as lead displacement, infection or pacemaker erosion, but it can also be because of a need for pacemaker upgrade (single to dual) or pacemaker replacement as a result of changed clinical needs or end of battery life.24 The complication rate associated with a reoperation is substantially higher than that associated with initial implantation.29
Costs associated with intervention
The cost of pacemaker implantation comprises several elements:
price of the generator and leads
implant procedure (setting and personnel)
personnel involved prior to and following implantation
regular routine follow-up
management of perioperative complications
management of late complications
replacement or upgrade at the end of the life of the pacemaker or in response to changing clinical need.
Further details on the costs associated with pacemaker implantation are given in Chapter 4, Costs.
