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AN AUDIT OF ELECTROPHYSIOLOGICAL SERVICES
AT MANCHESTER ROYAL INFIRMARY
1995 - 2000
Dr
Adam P Fitzpatrick MD FRCP FACC
Consultant Cardiologist
Dr Clifford J Garratt MD FRCP
Reader in Cardiology
Contents
Background
Electrophysiology Caseload and Referral Base
Results
Comparison with International Norms
Complications
Capital Investment
Benefits of Catheter Ablation
Future Need for Catheter Ablation
Implantable Defibrillators
Prescription of ICDs - MRI Experience
Survivorship after ICD Treatment
Treatment by ICDs - MRI Experience
Who Needs an ICD? - Published paper by Alan Fitchet & Adam Fitzpatrick
ReferencesThe last fifteen years have seen a dramatic change in the management of patients with heart rhythm disturbances.
In the past, patients with such problems could be treated only with anti-arrhythmic drugs. Such drugs are rarely fully effective, and have important side-effects, including the ability to cause new life-threatening rhythms. At the same time potential candidates for catheter ablation therapy may be at some mortal risk to life, in particular those with the Wolff-Parkinson-White syndrome 1.
Recently curative techniques have become available. In the 1980's surgical mapping and ablation techniques were perfected 2. In the 1990's this lead to the new technique of catheter ablation 3-5. Radiofrequency catheter ablation (RFCA) may now be used to treat, and in most cases cure, most abnormal rhythms, with a minimally invasive percutaneous approach and a short hospital stay. We started Day Case ablation in late 1998.
The most commonly treated arrhythmias are the Wolff-Parkinson-White syndrome, and AV Nodal Re-entrant Tachycardia. These two account for about 85% of the common cases of supraventricular tachycardia. With rapid development it has been possible to approach other arrhythmias. These include atrial flutter, atrial tachycardia and ventricular tachycardia.
The Trent Institute for Health Services research in it's Working Group Report on Acute Purchasing of Tertiary Cardiology published in December 1996 6 said that radiofrequency catheter ablation was, "one of the most effective therapies available in any sphere of medicine, and is curative with a 90% success rate, and a very low complication rate".
This document audits performance in electrophysiology services at Manchester Royal Infirmary between July 1995 and December 1999.
CASELOAD OF MANCHESTER HEART CENTRESince August 1995 we have undertaken 812 electrophysiological cases for patients with common benign and life-threatening arrhythmias. Included in this series are:-
510 patients have undergone 580 episodes of RFCA. Long-term procedural success has been achieved in 489 (96%) of cases.
- 50% male
- average age 35
- 87% referred electively by a consultant, 5% emergencies
- patients referred
from Greater Manchester but also, North Wales, Lancashire, Yorkshire,
South West of England. Patients also treated from Pakistan, India and
Greece.
The demographics of this population are:
Figure 1. Referral centres in North West Region and North Wales. RESULTS OF CATHETER ABLATION FOR SVT 1995-2000 - MRI SERIES
Procedure No Patients Successes % Cured WPW 165 145 139 96 AVNRT 176 168 167 100 approx Atrial Flutter† 79 59 45 76 Atrial Tachycardia 23 18 15 83 AV Junctional Ablation* 122 118 115 - Ventricular Tachycardia 15 11 8 72 Transseptal Approach 129 120 118 Key: WPW; the Wolff-Parkinson-White Syndrome, AVNRT; AV nodal re-entrant tachycardia.
Legend: Figure 2. gives the breakdown of diagnosis and results of treatment up to March 1999. Manchester Royal Infirmary has pioneered the use of the transseptal approach to catheter ablation of cardiac arrhythmias in the UK.
Important complications have occurred including:
13. accidental heart block requiring permanent pacing - 4 cases cardiac
14. tamponade requiring urgent percutaneous aspiration - 1 case
15. femoral neuropathy - 1 case
USA Registry MRI Series
Ablation Procedure Patients % Success % Patients %
Success % WPW Right 92 8 83 90 9 6 7 78 WPW Left 270 26 257 95 102 20 98 96 WPW Septal 40 4 39 98 14 10 14 100 WPW Posteroseptal 98 9 86 88 14 10 13 93 AVNRT 373 36 362 97 168 33 167 99 AV Junction Ablation 121 12 121 100 118 23 115 97 Key: WPW Right; accessory pathway located along right ventricular free wall, WPW Left; ; accessory pathway located along left ventricular free wall, WPW Septal; accessory pathway located on the interventricular septum, WPW posteroseptal; accessory pathway located in the posterior triangle, AVNRT; AV nodal re-entrant tachycardia.
Legend: Figure 3. This table compares the MRI catheter ablation results with those recorded in a 17 centre study in 1050 patients, mean age 37 years, funded by the National Institutes of Health in the USA and undertaken between 1992 and 1995.
COMPARISON WITH INTERNATIONAL NORMSCOMPLICATIONS
USA Registry MRI Series
Complication Type Patients % Patients % Death 3 0.3 0 0 Stroke 2 0.2 0 0 Complete AV Block* 10 1 4 1.3 Other AV Block 21 2.0 3 1 Tamponade 6 0.6 1 0.2 Valve Damage 1 0.1 0 0 Myocardial Infarction 1 0.1 0 0 Embolic Event 4 0.4 0 0 Pericardial Effusion 20 1.9 2 0.4 Pericarditis 4 0.4 2 0.4 Haematoma 32 3.05 16 3.1 Legend: Figure 4. This table compares the MRI catheter ablation complications with those recorded in a 17 centre study in 1050 patients, funded by the National Institutes of Health in the USA and undertaken between 1992 and 1995.
Investment in the Service.
The Central Manchester Healthcare Trust made significant capital investments in order to support the electrophysiology service.
Bi-plane catheter laboratory upgrade £160,000
Prucka CardioLab EP Recording System £70,000
Bloom Stimulator £19,500
Waiting List.
Most catheter ablation work can be done electively, but unmet need and a high prevalence has lead to very long waiting times throughout 1997-99. We currently have 18-month waiters booked two months ahead, and have been under this pressure since early 1998. Approximately 150 patients are currently waiting.THE BENEFITS OF CATHETER ABLATION
Some patients who are suitable for catheter ablation are at risk of sudden cardiac death. These are the patients with WPW who have accessory pathways capable of very rapid conduction. If atrial fibrillation occurs such pathways exhibit "all-or-nothing" conduction. This may lead to very rapid stimulation of the ventricles resulting in ventricular fibrillation and death 1.
For most other patients with SVT the principle impact is the effect on quality of life. For health care systems the principle impact is upon cost-effectiveness, since curative ablation is far more cost-effective for moderately symptomatic patients than medical treatment.
Bubien et al 7, systematically demonstrated the quality of life gain after catheter ablation for a wide range of patients with arrhythmias.
ATRIAL FIBRILLATION QUALITY OF LIFE US Norm A/Fib p< 75 58 0.01 61 24 0.01 84 34 0.01 81 7 0.01 81 28 0.01 83 41 0.01 75 45 0.01 72 48 0.01 Bubien et al Circulation 1996;94:1585-91
Legend: Figure 5. Using the quality-of-life instrument "SF-36", this graph compares quality-of-life in patients with atrial fibrillation and controls in a US population, showing a significant negative impact of atrial fibrillation.
ATRIAL FIBRILLATION QUALITY OF LIFE A/Fib 1mon 6mon p< 58 74 62 0.5 24 35 42 0.01 34 46 52 0.04 7 25 36 0.01 28 44 65 0.01 41 59 62 0.02 45 56 60 0.01 48 56 52 0.62 Bubien et al Circulation 1996;94:1585-91
Legend: Figure 6. Using the quality-of-life instrument "SF-36", this graph compares quality-of-life in patients with atrial fibrillation at baseline and 1 month and 6 months after palliation by catheter ablation of the AV junction followed by permanent pacemaker implantation. The statistical findings represent the minimum signficance found.
Kertes et al , compared the costs of medical treatment of SVT with catheter ablation treatment, finding that catheter ablation was cheaper over time.
Not all catheter ablation patients can be cured successfully without further long-term treatment, and some patients require a permanent pacemaker, a disadvantage noted by the Trent Institute 9. However, such treatment can be shown to be cost-effective for many patients, (see case studies below). Further, Fitzpatrick et al, have shown that quality of life is significantly improved even when a pacemaker has to be fitted as part of the treatment al 10. Twenty-three per cent of our patients have had such treatment.
FUTURE NEED FOR CATHETER ABLATION
The British Cardiac Society recommends that the need for catheter ablation services requires provision for at least 40 cases/annum/million year 11, when demand has reached a steady state. This is underlined by the findings of the 1999 Review of Tertiary Cardiothoracic Services for the North-West Region 12. The Trent Institute for Health Services 13, indicate that provision of 30 procedures/million should be made for a backlog of symptomatic individuals who will need treatment before referral rates are reduced. It is clearly this backlog of work that has lead to strains upon the electrophysiology service at the Manchester Heart Centre in the last few years, and will continue to keep demand high for the foreseeable future. Also, needs are calculated on the basis of ablation requirements for accessory pathways. Need will be greater with expanding indications for ablation of atrial and ventricular arrhythmias.IMPLANTABLE DEFIBRILLATOR THERAPY
BACKGROUND
Implantable defibrillators (ICDs) have been available for clinical use for nearly 15 years. Only recently, however, has the use of ICDs been supported by evidence from randomised controlled trials. The most important of these is the AVID trial 13. The re-print of this article is included in this appendix, and is referred to in the following pages under the title, "Who needs an ICD?".
The British Cardiac Society recommends and annual implant rate of 15 ICDs per million per year. This rate is also underscored by the findings of the recent Regional Review of Cardiothoracic services al 12. This rate is also acknowledged in the Trent Institute for Health Services research in it's Working Group Report on Acute Purchasing of Tertiary Cardiology in December 1996 15.
MANCHESTER HEART CENTRE EXPERIENCE 1994-99At the Manchester Heart Centre we have recorded an ICD implant rate of approximately 20 new cases/year between 1996 and 1998. Implant rates are expected to rise in 1999 as some patients who have survived require an ICD generator change due to battery depletion. Such patients may eventually add 10-15 cases/year to a background rate of 20/year at this centre.
Legend: Figure 12. This table shows implantation rates for ICDs at Manchester Royal Infirmary between 1995 and 1998. Rates remain well below conservative guidelines provided by the British Cardiac Society, and more recent guidelines from NICE.
SURVIVAL WITH AN IMPLANTABLE DEFIBRILLATOR
Survival of patients at the Manchester Heart Centre is compared below with ICD patients in the AVID trial and "best medical therapy" patients using Kaplan-Meier survival statistics.
Legend: Figure 13. This table compares the survival of patients with ICDs at Manchester Royal Infirmary, ICD treated patients in the NIH-sponsored Anti-arrhythmics versus Implantable Defibrillator (AVID) study and drug-treated patients in the AVID study.
TREATMENT WITH ICDs - MRI EXPERIENCE
Prescribing ICD therapy requires a judgement about the likelihood of patients with sudden cardiac death or life-threatening ventricular arrhythmias suffering a life-threatening recurrence. Some patients with very severe heart disease, especially when there is heart failure or very poor left ventricular function, may be more likely to die of underlying heart disease than of an arrhythmia. Other patients may have life-threatening co-morbidity, e.g. cancer. Other patients might receive an ICD, but never be treated by it. The prescribing of ICDs must take all these factors into account. Selection of patients should be directed at treating patients with a relatively high risk of recurrence, but who are also likely to have a reasonably long life of good quality with an ICD, and not a short life of poor quality. We have reviewed our ICD patients to look at use of the ICD. This is expressed below as arrhythmia recurrence-free survival, indicating that a high proportion of our patients receive successful treatment within a short follow-up of implantation.
Legend: Figure 14. This table gives a Kaplan-Meier curve for survival free of successful, appropriate ICD treatment. During this time 5 patients have died, 3 from heart disease, 2 from non-cardiac causes.
The following article was published in Hospital Medicine in June 1999. Also included is the full text of the NIH-sponsored Anti-arrhythmics versus Implantable Defibrillators Trial (AVID).
It is concluded from the above data and the accompanying articles that ICDs have a confirmed role in the management of patients with life-threatening arrhythmias. MHC patients are carefully selected and do well in comparison with patients in major trials. At Manchester Royal Infirmary, an implant/generator-change rate of 30-50 cases per annum should be anticipated.
Who needs an implantable defibrillator.
Alan Fitchet, Adam P Fitzpatrick
Dr Alan Fitchet is Specialist Registrar in Cardiology and Dr Adam Fitzpatrick is Consultant Cardiologist at the Manchester Heart Centre, The Royal Infirmary, Manchester M13 9WL.
Correspondence to Dr AP Fitzpatrick.Ventricular arrhythmias account for 80% of sudden cardiac deaths. The implantable defibrillator (ICD) is an effective means of preventing these deaths. This article discusses which patients may benefit from ICD implantation and addresses the cost-effectiveness of their use.
Sudden cardiac death (SCD) kills 90,000 adults per annum in the UK. Observational data suggest that survivors from arrhythmic death suffer a recurrence rate of 30-50% within 2 years. Recent studies suggest that the best way of preventing such patients from subsequently dying of a recurrence may be the use of an implantable defibrillator (ICD). In spite of this, many patients in the UK receive no specific treatment or antiarrhythmic drug (AAD) treatment alone. Key Points
The implantable defibrillator (ICD) has a defined role in secondary prevention of sudden cardiac death but its use in primary prevention remains under debate.
THE ROLE OF AAD THERAPY
Because most sudden death episodes occur in patients who have ischaemic heart disease and have suffered a previous myocardial infarction (MI), drug trials aimed at reducing arrhythmic death in this group are relevant in considering the role of ICD therapy.
Randomized placebo-controlled trials of class I AADs, such as flecainide, which were designed to show a reduction in subsequent arrhythmic death, unfortunately showed an excess of deaths in patients after MI (Echt et al, 1991). It is widely believed that all class 1 agents have a similar deleterious effect. Indirect evidence for this comes from the ESVEM study (Mason and the ESVEM Investigators, 1993), where a number of class 1 agents were used to treat ventricular arrhythmias, and all performed very poorly in comparison with sotalol. Unfortunately, in the SWORD (Survival with oral d-sotalol) study (Waldo et al, 1996), sotalol was also shown to increase mortality over placebo when prescribed post-MI, and is no longer licensed in the UK for use in such patients.
As a result of these drug failures, amiodarone is currently considered the most effective AAD. However, the benefits after MI are not clear. Small non-randomized, non-controlled trials comparing amiodarone with 'conventional medical therapy' (usually involving the use of class 1 agents) as a primary preventative agent, after MI, have suggested a benefit from amiodarone. However, in larger randomized, placebo-controlled studies such as EMIAT (European myocardial infarct amiodarone trial) (Julian et al, 1997), the benefit almost disappears (Figure 1; Sim et al, 1997). In EMIAT amiodarone did reduce arrhythmic death in patients with impaired left ventricular function after MI, but all-cause mortality was not significantly different from placebo.
Use of amiodarone in secondary prevention is more promising but remains limited. In the CASCADE (Cardiac arrest in Seattle: Conventional vs Amiodarone drug evaluation) study (Greene and the CASCADE Investigators, 1993) patients who had survived out of hospital ventricular fibrillation (VF) were randomized to receive either empirical amiodarone (n=113) or class 1 AADs guided by electrophysiological (EP) study (n=115). Nearly half (105) also received an ICD. Most had suffered a previous Ml and half had a history of congestive cardiac failure with an overall mean left ventricular ejection fraction (LVEF) of 35%. Survival free of cardiac death, resuscitated VF or defibrillation at 2,4 and 6 years was 82%, 66% and 53% with amiodarone and 69%, 52% and 40% with conventional drug therapy respectively (p=0.007). Although the amiodarone treated group had a significantly better outcome, their overall mortality remained high and discontinuation of treatment in this group was substantial because of serious side-effects such as thyroid disease and pulmanory toxicity. This trial further underlines the poor outcome to be expected with class I AADs, which now have no place as the sole management of patients with a risk of SCD.
In the aforementioned studies, amiodarone was prescribed empirically. Wailer et al (1987) investigated the role of EP study assessment of AAD therapy efficacy in predicting future arrhythmic events and mortality. Two hundred and fifty eight patients with inducible ventricular arrhythmias underwent serial EP studies after loading with AAD treatment. The majority received amiodarone. They were placed into 3 groups according to whether the AAD rendered the arrhythmia non-inducible (group 1), beneficially modified it (group 2) or had no beneficial effect (group 3).
Total mortality and SCD over a follow-up of 0.1-57.4 months were reduced in groups 1 and 2 at 13% and 12% respectively compared with group 3 at 39%. Arrhythmia reoccurrence was more frequent in group 2 compared with group 1 (39% vs 7%), but mortality did not differ (Figure 2). This suggests an important role for EP assessment of AAD efficacy in patients with symptomatic ventricular arrhythmias, identifying those who remain inducible (who do badly), and those who are not inducible and do well. Waller's study also shows that patients who remain inducible fall into two groups Some patients have an apparent benefit from treatment, with slowing and better toleration of induced ventricular tachycardia (VT). Others have no benefit These two groups unfortunately comprise the vast majority of amiodarone-treated patients undergoing EP study after loading with the drug. Outcome studies show that both groups have a high rate of reoccurrence of VT, although this is much less often fatal in the group who have some benefit from the drug
Beta-blockers have an established role in reducing SCD when prescribed empirically after MI (Norwegian Multicenter Study Group, 1981), but their role in secondary prevention in patients with previous ventricular arrhythmias has not been formally investigatedEVOLUTION OF THE ICD
Clearly, AAD's have severe limitations and may have harmful effects in patients at high risk of SCD. Long before this was fully appreciated, however, work had begun in Israel, and subsequently the USA, on a fully implantable, automatic, internal defibrillator. Pioneering work was done by Mirowski and colleagues (1970), leading to approval for human use in the USA in l985. At this time devices were Crude, had few programmable features, no ability to store and retrieve episodes, and had to be implanted via a thoracotomy using large shocking leads sutured directly to the epicardial surface of the heart. Reductions in generator size (Figure 3) and use of trans-venous lead systems currently allow implantation in the infraclavicular region either subcutaneously or submuscularly below the pectoralis major. Catheter laboratory implants by cardiologists were first described by Fitzpatrick et al (1994). Patients are often anaethetized but a series of successful implants under local anaesthetic and conscious sedation have been reported (Lipscomb et al, 1998).
A typical device consists of a single lead inserted through the cephalic or subclavian vein into the right ventricular apex with a high voltage circuit between a right ventricular coil (cathode) and the generator can (anode) (figure 4). Modern devices allow a variety of treatments to be programmed into the device and subsequently delivered automatically from bradycardia pacing, anti-tachycardia pacing of VT to DC cardioversion/defibrillation of VT and VF as necessary. The latest generation if ICDs incorporate duel chamber lead systems that facilitate greater accuracy in arrhythmia detection and diagnosis plus atrioventricular sequential pacing when needed.
However, ICD's are very costly; and debate continues as to which patent groups will benefit from ICD implantation, how they may be selected and how the cost implications should be addressed.
THE ICD IN SECONDARY PREVENTION
Three randomized prospective trials have compared the ICD with AAD therapy in subjects with previous life-threatening ventricular arrhythmias. These have reported within the last 2 years and have showed a significant survival advantage in the ICD-treated groups. The most important of these trials was the National Institutes of Health-sponsored AVID (Antiarrhythmics vs implantable defibrillators) trial (AVID Investigators, 1997) which compared ICD (n=507) with either empirical amiodarone (n=496) or 'guided' sotalol (n=13). Patients randomized had survived an episode of VF, suffered an unexplained syncopal episode and then exhibited inducible VT during EP study, or presented with VT resulting in haemodynamic compromise m the presence of LVEF of <=40%. A response to sotalol was guided by Holter monitoring or EP study. Sotalol was prescribed to few patients either because of its failure to suppress ventricular arrhythmias or because of concerns over its use in the presence of impaired ventricular function.
Follow-up took place over 3 years (mean 18.2+/-12.2 months), and showed a significant reduction over this period in the primary end point of mortality in the ICD-treated group of 31% (absolute 24.6% vs 35.9%). Significantly mortality benefits (38% reduction) were seen within 12 months (figure 5). A criticism of the AVID trial is the increased use of Beta-Blockers in the ICD group compared with the amiodarone-treated patients (45% vs 13%,) but, following a sub-study to correct for this bias, a significant benefit remained.
The CIDS (Canadian implantable defibrillator study) trial (Dorian et al, 1994) used similar patient inclusion criteria as AVID. Patients were randomized to ICD (n=328) or amiodarone (n=331) and followed up for 3 years. Mortality was reduced by 20% (absolute 25% vs 30%) in the ICD treated group.
Click on image to see larger versionThe CASH Study (Cardiac arrest study of Hamburg) (Siebels and Kuck, 1994) studied survivors from VP alone and randomized them to ICD (n=99) or AAD with amiodarone (n=92), metoprolol (n=97) or propafenone (n=58). The propafenone arm was stopped early because of an increased mortality rate. Follow-up over 2 years showed a 37% (absolute 12.1% vs 19.6%) reduction in mortality in the ICE) group compared with the amiodarone or metroprolol groups. These trials make the case for the use of ICDs rather than best available medical therapy in patients who have had an episode of life-threatening ventricular arrhythmia. However, they do not evaluate the role of treatment with amiodarone guided by EP study vs ICD. They also do not directly address issues of cost-effectiveness.
THE ICD IN PRIMARY PREVENTION
Two randomized trials have investigated prophylactic use of ICDs, based on the rationale that patients with impaired left ventricular function are at increased risk of SCD) in the absence of prior documented substantial VT or VF.
The MADIT trial (Multicenter Automatic Defibrillator Implantation Trial) (Moss et al, 1996) enrolled patients who had sustained a recent (>=3 weeks before enrolment) MI and subsequently had a LVEF <=35%. Patients had to have non-sustained VT on Holter monitoring in order to be considered, and then had to undergo EP study testing. At HP study, in order to be randomized patients had to exhibit inducible VT or VF that was not suppressible with intravenous pro-cainamide. Such patients were then randomized to ICD (n=95) or 'conventional' therapy (n=101). Conventional therapy was at the physician' discretion and resulted m prescription of amiodarone to 45% and Beta-blockers to 5% of these patients. The trial was terminated prematurely at 2 years after enrolment of 75% of the planned total number of patients because of an observed 54% reduction in mortality (absolute 15.8% vs 38.6%). The timing of termination was dependent on a sequential monitoring statistical algorithm, designed to minimise the number of deaths required to obtain a statistically significant conclusion. This had the disadvantage of limiting the number of subjects available for the sub-group analysis. Examination of cause of death suggested that ICD reduced not only arrhythmic death (13 vs 3) but also non-arrhythmic cardiac death (13 vs 7) and death of unknown causes (6 vs 0), a finding which may be a result of inaccurate reporting, but is not fully explained. Once again there was an excess of Beta-blocker use in the ICD group (27 vs 5) by correcting for this using Cox regression analysis did not account for their improvement in survival.
The rationale for the coronary artery bypass grafting (CABG) patch trial (Bigger et al, 1997) was developed at a time when thoracotomy was required for ICD implantation. Patients undergoing CABG with an abnormal signal-averaged electrocardiogram and LVEF <=35% were randomized to receive an ISD (n=446) or not (n=454) at time of surgery. There was no significant difference in mortality between the two groups after 32 months of follow-up: 22.6% in the group with an ICD and 20.9% in those not receiving an ICD. It has been suggested that the difference in results between MADIT and CABG-patch might have been because the more rigorous screening in MADIT selected out a population at higher risk of SCD, or possibly that revascularisation of all patients in CABG-patch reduced this risk universally.WEAKNESSES OF A PROGRAMME Op PRIMARY PREVENTION WITH ICDS
There are two major problems with the use of ICDs in primary prevention of death caused by life threatening ventricular arrhythmias. The first is that all methods of risk stratification of patients for such arrhythmias are imperfect. Combining the beet methods only gives a 50% positive predictive accuracy. This is no better than the toss of a coin an individual patient The positive predictive accuracy rises with the specificity of any screening process, but at the expense of sensitivity. This results in patients who will have events missing out on treatment became they do not fulfil all entry criteria. Also, in spite of best efforts to secure a screening process that achieves the highest positive predictive accuracy, some asymptomatic patients would receive treatment they had not sought, and did not need, which might be harmful to them if implant or other complications arose. Such instances raise ethical concerns about ICD therapy for primary prevention.
The second major problem arises from the cost of such a programme of primary preventive treatment with ICDs. Cost analysis provided for MADIT (Muslilin et al, 1998) calculated a cost effectiveness ratio of $27000 per life year saved compared to conventional treatment. This fell to $23000 if transvenous defibrillators had been used in place of surgically implanted ICDs. However, this did not account for the costs of screening. MADIT succeeded in randomizing just 200 patients from 31 centres in 5 years. Centres were chosen for their high volume of work, but, in spite of this, the exhaustive evaluation process resulted in few suitable patients being found. Patients could not be screened until at least 3 weeks after their index MI. All patients therefore required outpatient echocardiography and Holter monitoring, and many required costly EP study before any could be identified randomization.
Such issues as these provide arguments against a programme of ICD implantation for the primary prevention of death from life threatening ventricular arrhythmias.COST IMPLICATIONS OF SECONDARY PREVENTION WITH ICDS
The typical cost of an ICD and transvenous leads in the UK is £20,500 excluding implantation and follow-up costs. Understandably, much interest has been directed at assessing the cost-effectiveness of ICD implantation in different patient groups. The majority of this work has been performed in the USA.
Wever et al (19%) performed a cost-effectiveness analysis of the use of ICDs for secondary prevention. It assessed health-care costs in a prospective study of survivors of cardiac arrest complicating previous MI with documented VT or VE. These were randomized to early ICD (n=29) or EP-guided AAD therapy (n=31). Map-guided VT surgery was performed in 5 of the EP-guided AAD group, almost doubling the cost of treatment compared to those treated with AAD alone
($44 100 vs $23 500). VT surgery is not commonly performed in the UK at present as few, select patients may benefit Almost half of the EP-guided AAD patients received an ICD by the end of the study. A net saving of $11,315 per patient per year alive saved was attributed to having an ICD as first choice therapy. Patients discharged on AAD done had lowest total costs but an unusually high mortality (7 out of 11), translating to a poor cost-effectiveness of $196 per day alive compared to $63 per day alive for the ICD group. Length of time spent in hospital, change of AAD medication and number of invasive procedures all improved favourably in the ICD treated group.
Owens et al (1997) wed a hypothetical cohort model to estimate cost-effectiveness of ICD implantation compared with amiodarone treatment. SCD rate at 1 year on amiodarone was estimated at 8.6% for 'high risk' Patients, using published data, and it was assumed that ICD reduced these rates by 20-40% per annum. Assuming a generator battery life of 4 years, the marginal cost-effectiveness ranged from $74,400 per quality-adjusted life year gained (if ICD reduced the SCD rate by 20%) to $37,300 per quality-adjusted life year gained (if ICD reduced the SCD rate by 40%). At the 30% effectiveness level the marginal cost-effectiveness was $49,300 per quality-adjusted life-year gained.
An interesting finding was that if patients were treated initially with amiodarone, and then required ICD because of recurrent ventricular arrhythmia, costs were increased compared with the other two groups. Life expectancy was similar to the amiodarone-only group, resulting in a poor marginal cost effectiveness. In keeping with other trials, it may be that if an ICD is necessary it should be implanted early. Currently, there is no consensus about acceptable levels of cost effectiveness, but $50,000 (£31,250) per quality adjusted life-year gained is generally regarded as significant (Figure 6 shows cost-effectiveness comparisons for established medical treatments).
(click on image to see larger version)At this cost, using the data from Owen's study, ICD therapy would need to be targeted to achieve a 30% reduction in all cause mortality, without a reduction in quality of life. Advances in battery technology and increased ICD longevity should further improve cost effectiveness. We await publication of the quality of life and economic data from the recently reported randomized prospective trials, in particular the AVID trial, which included these as secondary end-points.
INDICATIONS FOR ICD TREATMENT
In the light of the findings of recent randomized trials of ICD treatment, and the arguments above, it is possible to make some suggestions for the use of this costly and controversial technology.Sudden cardiac death
An ICD should be recommended if a patient presents with SCD caused by VF where acute ischaemia can be excluded, cardiac failure resulting from impaired left ventricular function is not a major feature (since it confers a poor overall prognosis), and VF has not apparently degenerated from VT. Where VT was clearly the initial or index arrhythmia, the patient should undergo EP study with programmed ventricular stimulation to assess the response to amiodarone.Life-threatening ventricular arrhythmias
Where a patient presents with life-threatening VT with syncope or severe haemodynamic compromise, EP study should be undertaken to demonstrate.
whether amiodarone can suppress VT or render it less hazardous. If not, an ICD should be recommended. In patients treated with amiodarone who have recurrent hospital admissions with non fatal reoccurrences of sustained VT, an ICD should be considered where it is likely that antitachycardia pacing with back-up cardioversion/defibrillation would prevent further hospitalisations.Primary prevention
Screening patients using methods of risk stratification increases positive predictive accuracy but reduces sensitivity. This ensures that patients treated are drawn from groups that convey a higher apparent risk of later life-threatening arrhythmias or SCD. However, many patients who will have a later episode are excluded by the screening process.
Furthermore, imperfect specificity ensures that many patients without symptoms will be subjected to the risks and costs of screening and treatment, but will not go on to have a clinical episode. These considerations, coupled with uncertainty about the MADIT findings, the very small numbers of patients available using MADIT criteria, and the vast cost involved, would presently appear to make ICDs for primary prevention of SCD impractical in the UK.Special groups
Patients who have severely impaired ventricular function and who are awaiting cardiac transplantation, but suffer from the dearth of suitable donor organs, have a high rate of SCD (approximately 30%). This can be effectively prevented by the use of ICDs, enabling many patents to survive to transplantation who would otherwise die. In this group ICDs can be used as a 'bridge to transplantation' (Sweeney et al, 1995).
Patients with primary electrical disease, such as the congenital long QT syndrome and the Brugada syndrome (Brugada and Brugada, 1992), may have a high risk of SCD. An ICD may normalize their prognosis.
Patients with a very severe family history of SCD, and yet no way of assessing risk or individual involvement in the condition should increasingly be considered for an ICD. As the risk of treatment declines to very low levels with implantation under local anaesthesia (mortality <0.5%) of devices the size of a pacemaker, it becomes harder justify non-treatment to patients with a very high apparent risk, whose individual involvement cannot be excluded. Fortunately for healthcare systems, these patients are very rare.1. Klein G J Bashore T M Sellers T D et al Ventricular fibrillation in the Wolff-Parkinson-White syndrome N Eng J Med 1979; 301:1080-1084
2. Gallagher J J Pritchet ELL Sealy WC et al The pre-excitation syndrome
Prog Cardiovasc Dis 1978; 20 (4): 285-299
3. Jackman WM, Wang X, Friday KJ, Roman CA, Moulton KP, Beckman KJ,
McClelland JH, Twidale N, Hazlitt HA, Prior MI, Margolis PD, Calame JD, Overholt ED, Lazzara R. Catheter ablation of accessory atrioventricular pathways (Wolff-Parkinson-White syndrome) by radiofrequency current. N Engl J Med 1991; 324: 1605-1611.
4. Calkins H, Langberg J, Sousa J, El-Atassi R, Leon A, Kou W, Kalbfleisch S, Morady F. Radiofrequency catheter ablation of accessory atrioventricular connections in 250 patients: abbreviated therapeutic approach to Wolff-Parkinson-White syndrome. Circulation 1992; 85: 1337-1346.
5. Kuck K-H, Schluter M, Giger M, Siebels J, Duckeck W. Radiofrequency current catheter ablation of accessory atrioventricular pathways. Lancet 1991; 337: 1557-1561.
6. Trent Institute for Health Services Research, Universities of Leicester, Nottingham and Sheffield: Guidance note for Purchasers 1996 2nd Edition Chapter 2.6 pp 14
7. Bubien R S Knotts-Dolson S M Plumb V J Kay G N Effect of radiofrequency catheter ablation on Health-related quality of life and activities of daily living in patients with recurrent arrhythmias
Circulation 1996; 94: 1585-1591
8. Kertes PJ, Kalman JM, Tonkin AM Cost effectiveness of radiofrequency
catheter ablation in the treatment of symptomatic supraventricular tachyarrhythmias Aust N Z J Med 1993 Aug;23(4):433-436
9. Trent Institute for Health Services Research, Universities of Leicester,
Nottingham and Sheffield: Guidance note for Purchasers 1996 2nd Edition
Chapter 3.5 pp 18
10. Fitzpatrick A P Kourouyan H D Siu A Lesh M D Griffin J C Scheinman M M Quality of life and outcome after radio-frequency catheter ablation of the AV junction and permanent pacing Am Heart J 1996; 131: 499-507
11. The changing interface between district hospital cardiology and the major cardiac centres. Heart 1997 Nov;78(5):519-23
12. North West Regional Review of Cardiothoracic Services 1999.
13. Trent Institute for Health Services Research, Universities of Leicester,
Nottingham and Sheffield: Guidance note for Purchasers 1996 2nd Edition Chapter 2.6 pp 14
14. Zipes DP, The AVID investigators ( 1997) A comparison of
antiarrythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 337: 1576-1583
15. Trent Institute for Health Services Research, Universities of Leicester, Nottingham and Sheffield: Guidance note for Purchasers 1996 2nd Edition Chapter 2.6 pp 14
