The clinical effectiveness of the implantable cardioverter defibrillator (ICD) in selected high-risk populations is well documented. The past, present and future of ICD therapy is discussed
Dominic Kelly MD
Mark Sopher MBBS MRCP MD
Dorset Cardiac Centre,
Royal Bournemouth Hospital,
The clinical effectiveness of the implantable cardioverter defibrillator (ICD), in selected high-risk populations, has been demonstrated in several large-scale clinical trials. Since the first human implant in 1980, vast advances in technology have allowed improvements in device and lead design, rhythm recognition and therapy delivery. In addition, the indications for implantation have been further delineated, leading to a rapid rise in worldwide ICD usage. Current technology continues to exert limitations that could be resolved by further development or alternative approaches to cardiac defibrillation. This article discusses the past history, current status and potential future advances of ICD therapy.
The ICD has revolutionised the treatment of patients at risk of sudden cardiac death due to ventricular tachy-arrhythmias. The concept of the ICD was first developed by Michel Mirowski (Baltimore, USA), and was prompted by the sudden death of his colleague, Professor Harry Heller. The first human implant was performed in 1980 and approved by the US Food and Drug Administration (FDA) in 1985.1 Early ICD systems were epicardial, requiring thoracotomy for implantation with pulse generators that were large and bulky, requiring abdominal implantation. Since then there has been widespread and extensive research and development of the ICD, leading to robust trans-venous systems with smaller generators and enhanced rhythm recognition and therapy delivery.
Current practice is based on published large-scale clinical trials. Initial studies focused on the use of ICD therapy as secondary prevention in those patients with aborted sudden cardiac death (SCD). Three large-scale clinical trials have demonstrated reductions in mortality in this population. The Antiarrhythmics Versus Implantable Defibrillators (AVID) trial enrolled patients with prior cardiac arrest or haemodynamically significant, sustained ventricular tachycardia (VT) and randomised patients to either ICD implantation or anti-arrhythmic drug therapy.(2) The AVID trial was terminated prematurely because of improved survival rates in the ICD-treated patients. Later the superiority of ICD therapy in secondary prevention was confirmed in both the Cardiac Arrest Study Hamburg (CASH)(3) and the Canadian Implantable Defibrillator Study (CIDS).(4) These trials firmly established the ICD as preferred therapy in patients who have survived cardiac arrest or haemodynamically significant, sustained VT.
Indications for ICD therapy have been further expanded following several studies demonstrating significant survival benefit for primary prevention in patients with high-risk features for malignant arrhythmias. MADIT I enrolled patients with ischaemic cardiomyopathy (left ventricular ejection fraction (LVEF) ≤35%) and asymptomatic, non-sustained VT who had inducible sustained VT or ventricular fibrillation (VF), and although terminated early, demonstrated a clear survival benefit in those patients receiving ICDs over standard medical therapy.(5) This data was replicated in the MUSTT study, which enrolled patients with similar criteria and randomised patients to therapy guided by electrophysiological studies (EPS) versus no specific anti-arrhythmic therapy, and showed survival benefit in the EPS-guided group attributable to the ICD.(6) Moreover, the larger MADIT II (Multicenter Automatic Defibrillator Implantation Trial II)(7) study demonstrated a 31% reduction in mortality rate in patients with prior myocardial infarction and LVEF at or below 30% who received an ICD over standard medical therapy, including a high percentage use of beta blocker therapy
The survival benefit with ICDs has also been demonstrated in subjects with non-ischaemic cardiomyopathy. The SCD-HEFT study included patients with impaired LV function due to both ischaemic and non-ischaemic aetiology. Results show that the mortality benefits of ICDs are evident in both aetiologies.(8)
Limitations and developments of current therapy
Despite powerful clinical evidence, there is no doubt that limitations exist in the current era of ICD therapy. In general, these limitation may be dichotomised into those related to device hardware or those related to rhythm recognition and therapy delivery.
Despite significant miniturisation of electronics, battery and capacitors included within the ICD generator, there remains problems related to the size and weight of ICD devices. Moreover, current battery technology often requires several generator replacements over a patient lifespan. Device size is especially of relevance to patients who are small or thin and in patients with concerns over cosmetic appearance. Efforts continue to reduce ICD generator volumes alongside optimisation of device shape to achieve more favourable cosmetic appearances and reduce erosion risk. In addition, newer technologies, such as the use of manganese-based batteries, may prolong device longevity with an associated reduction in revisions.
Limitations of trans-venous defibrillator leads are abundant. First, the presence of leads within the vasculature induces local fibrosis leading to vessel occlusions and collateral vessel formation. This may cause symptomatic problems and lead to difficulty if new leads are required. Second, ICD leads are subject to a significant degree of repetitive stress due to the dynamic movement of the heart. In the 1990s, it was observed that ICD leads were associated with a greater than expected failure rate compared to pacemaker leads.(9) Recent experiences of leads withdrawn from commercial sales due to unacceptable failure rates, with potential implications on patients’ health and wellbeing, have highlighted these limitations.(10) Thirdly, the presence of trans-venous leads poses a significant risk in the event of the need for removal such as in the context of device infection; ICD lead extraction being associated with a significant rate of morbidity and mortality.(11)
In the context of the significant limitations associated with trans-venous leads, attempts have been made to develop extra-vascular, ICD systems. Recently the development of a subcutaneous ICD (S-ICD) system (Cameron Health) with rhythm recognition and defibrillator efficacy akin to that of trans-venous systems has cast hope on the future of extra-vascular ICDs(12) The S-ICD system is designed for ease of use and simplicity of patient management. These devices comprise a subcutaneous generator, combined with a tunnelled subcutaneous lead with surface ECG sensing (Figure 1). Limitations with the current generation of S-ICDs include generator size and the inability to provide pacing for bradycardia or tachycardia (ATP).
Inappropriate or unnecessary shocks
One of the risks of ICD therapy is that of inappropriate or unnecessary shocks. Inappropriate shocks may be defined as the delivery of a high voltage shock due to the inaccurate interpretation, by the ICD, of received electrocardiograms as a malignant ventricular arrhythmia. Inappropriate shocks may occur in the context of non-life-threatening tachycardia, such as atrial fibrillation with rapid ventricular response, or may occur due to the misinterpretation of received signals such as those associated with electro-mechanical interference or over-sensing of far field electrograms, Unnecessary shocks are high voltage therapies delivered for malignant ventricular arrhythmias that might otherwise have self terminated or terminated with anti-tachycardia pacing.
Recent data have demonstrated that ICD shocks, whether appropriate, inappropriate or unnecessary, are associated with impairment in quality of life and prognosis. The experience of the patient receiving a high voltage shock while fully conscious is highly unpleasant and may be associated with long term psychological worriment. Both inappropriate and unnecessary shocks are common. In the SCD-HEFT study approximately 16% of study participants received inappropriate shocks over the follow up period.(8)
Reduction of both inappropriate and unnecessary shocks has been the focus of several research groups and ICD manufacturers. The development of anti-tachycardia pacing (ATP) allows the treatment of many arrhythmias with painless, overdrive pacing bursts, and which terminates a large percentage of malignant arrhythmias. The Painfree II study demonstrated that almost three-quarters of fast ventricular tachycardia episodes (rate 188–250bpm) may actually be terminated by ATP, potentially avoiding unnecessary shocks. Delaying shock therapy by increasing detection times also has been shown to reduce shock therapies and could allow a percentage of arrhythmias to self-terminate.(13)
Further refinement of ICD algorithms to improve rhythm discrimination and optimise therapy delivery, while reducing inappropriate and unnecessary shocks, may further augment therapy through ICDs in their current format. In addition, expansion of the volume of stored data downloadable from the device may facilitate optimisation of patient wellbeing. For example, at present ICD therapy may be combined with biventricular, cardiac resynchronisation therapy (CRT) in patients with left ventricular dysfunction and electrical or mechanical dyssynchrony.
Diagnostic data in this cohort of patients may also allow optimisation of heart failure status. Current generation devices provide data on patient features such as heart rate variability, patient activity and transthoracic impedance which may allow identification of patients with worsening heart failure or imminent decompensation. Further refinement of these features may improve sensitivity and specificity and several large scale clinical trials are currently underway to investigate the benefit of such diagnostic information. Furthermore, the combination of ICD with other devices aimed to provide accurate heart failure diagnostic information, such as pulmonary artery or left atrial pressure sensors, may further establish these benefits.
Remote modelling systems
The introduction of remote monitoring systems, such as CareLink (Medtronic) Merlin (St Jude Medical) and Latitude (Boston Scientific), allows patients to upload device diagnostic data over secure web based transfers to create a ‘virtual clinic’. Remote programming, that is the programming of a device from a central hub while the patient remains at home, is currently limited by concerns over maleficent or inadvertent, inappropriate changes to patient’s ICD programming. Improvements in internet security will almost certainly allow this facility to advance. The emergence of both remote downloads and programming should, in theory, terminate the requirement to attend hospitals or clinics for device follow up.
Further miniaturisation of ICD generators through improvements in battery and capacitor technology should allow more favourable designs. In addition, refinements in lead design should minimise complications related to transvenous leads. Of significant interest is the emergence of the S-ICD. As discussed above, this technology is currently limited by both the generator size and the inability to provide ATP. The S-ICD is currently in the final stages of FDA approval having achieved panel recommendation for approval in April 2012. It is likely that once FDA approval is achieved, there will be active development of generator technology allowing significant reductions in volume of the device. 2013 is likely to see the first human implants of completely leadless pacemakers. These self-contained devices are implanted into the heart using catheter based delivery systems. One can envisage a time when the S-ICD is combined with a leadless pacing system to allow both high voltage shocks through the subcutaneous device and ATP through the leadless pacemaker, controlled through wireless connection.
Finally, the benefits of ICD systems are related to the sensitivity and specificity of the selection process for implantation. Improvements in the understanding of the pathophysiology of malignant ventricular arrhythmias and identification of novel markers of risk may allow improved patient selection and a more targeted approach to ICD implantation.
The clinical effectiveness of ICD therapy in selected populations has been well documented. Since the first implant in 1980, there have been vast advances in technology. Indications for ICD therapy have been delineated, leading to a rapid rise in worldwide ICD use. Current technology has limitations that should be the target of future developments in ICD technology.
- Mirowski M et al. Termination of malignant ventricular arrhythmias with an implanted automatic defibrillator in human beings. N Engl J Med 1980;303:322–4.
- AVID Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. N Engl J Med 1997;337:1576–83.
- Kuck KH et al. Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest : the Cardiac Arrest Study Hamburg (CASH). Circulation 2000;102:748–54.
- Bokhari F et al. Long-term comparison of the implantable cardioverter defibrillator versus amiodarone: eleven-year follow-up of a subset of patients in the Canadian Implantable Defibrillator Study (CIDS). Circulation 2004;110:112–6.
- Moss AJ et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 1996;335:1933–40.
- Buxton AE et al. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 1999;341:1882–90.
- Moss AJ et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877–83.
- Bardy GH et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225–37.
- Lawton JS et al. Implantable transvenous cardioverter defibrillator leads: the dark side. Pacing Clin Electrophysiol 1996;19:1273–8.
- Rao A et al. Sprint Fidelis 6949 high-voltage lead appears to be prone to early failure. Heart Rhythm 2008;5:167;author reply, 167.
- Hauser RG et al. Deaths and cardiovascular injuries due to device-assisted implantable cardioverter-defibrillator and pacemaker lead extraction. Europace 2010;12:395–401.
- Bardy GH et al. An entirely subcutaneous implantable cardioverter-defibrillator. N Engl J Med 2010;363:36–44.
- Wathen MS et al. Prospective randomized multicenter trial of empirical antitachycardia pacing versus shocks for spontaneous rapid ventricular tachycardia in patients with implantable cardioverter-defibrillators: Pacing Fast Ventricular Tachycardia Reduces Shock Therapies (PainFREE Rx II) trial results. Circulation 2004;110:2591–6.