Findings from the study showed a 45% reduction in mortality rates, 20% reduction in emergency admissions, 15% reduction in A&E visits, 14% reduction in elective admissions and 14% reduction in bed days.

Speaking at the launch of the Strategy for UK Life Sciences in London, Mr Cameron said the aim of the new campaign is to improve three million lives over the next five years.  “This is going to make an extraordinary difference to people,” he said. “Diabetics taking their blood sugar levels at home – and having them checked by a nurse.  Heart disease patients having their blood pressure and pulse rate checked – without leaving their home”.

“This is not just a good healthcare story. It’s going to put us miles ahead of other countries commercially too as part of our plan to make our NHS the driver of innovation in UK life sciences.”

SEHTA, the South East Health Technologies Alliance, has welcomed the announcement, having established its International Centre for Excellence in Telecare (ICE-T) in 2009.  “This is a very significant announcement and commitment which we welcome with open arms,” says Dr David Parry, CEO of SEHTA.  “Members of the ICE-T have for some time been developing a whole range of innovative products and services that are designed to help people live ways that suit them, their families, and those providing care”.

“Our members have also shown how telecare and telehealth can be of significant benefit, not just in terms of assisting people, but helping the NHS and other healthcare providers to achieve greater efficiencies and reduce their costs.”

“ICE-T members are ready to help deliver this commitment by government now that the case for telecare and telehealth has been proven through the Whole System Demonstrator,” he added.

And also…

Internet service improves care for newborns and chronically ill

Anna Gund, Chalmers University of Technology

The first dissertation² in the new research field of e-health at Chalmers University of Technology (Gothenburg, Sweden) has been completed, evaluating a new internet service developed at the University (Care@Distance).

Anna Gund, who publicly defended her doctoral dissertation recently, has worked with the new internet service including, a website where the chronically ill, or parents to newborns that require more careful follow-up, regularly fill in measurement values and other data related to their state of health.  Patients and care workers only need a computer or a smart phone with internet capability to use the system.

“Similar systems are tested now and again, with positive outcomes, but it seems to be hard to make them part of routine care,” says Gund. “We have developed a system based on the technology that is already used in most homes, and we believe that this can facilitate further dissemination”.

Care@Distance was tested in two groups: seniors with heart failure, and premature infants. Findings showed that staff actively embracing the technology and providing regular feedback on the information submitted by the patients was a key factor. 

“In cases where they have done so, patients were very positive and felt more secure and happy,” says Gund.

She has also performed a questionnaire survey regarding what care workers think about using telecare support in their work. It showed that they are generally very interested and have considerable confidence in the technology, but in practice some staff did not use the system as it was intended.  Anna Gund intends to find out why this was the case in her future research.

References

1 Whole system demonstrator programme: Headline findings – December 2011. Department of Health, 2011.  (Available from: http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_131684).

2 Gund A.  On the design and evaluation of an eHealth system for management of patients in out-of-hospital care.  Chalmers University of Technology, Gothenburg, Sweden 2011.  (Available from: publications.lib.chalmers.se/records/fulltext/77891.pdf).

Education and Training

There was an impressive timetable of educational sessions on a range of topics with eminent speakers, both national and international. The sessions included entertaining debates among experts and opinion leaders on some of the most controversial topics of today, such as the role of newer oral anticoagulants for stroke prevention in atrial fibrillation (AF).

For physician trainees there were the usual favourites such as ‘Cases and traces’ and ‘Diagnosing pacemaker and ICD traces’ – an excellent opportunity to discuss several challenging ‘real-life’ case studies across the range of heart rhythm conditions. The interactive ‘Hands-on’ and ‘How to’ sessions were as usual popular among trainees in particular – the former providing the opportunity to learn practical skills such as device programming on simulators with one-to-one supervision, and the latter covering important generic topics integral for career progression and academic excellence that are rarely taught during clinical training. Similar to last year, the HRUK accreditation course was held over three days, aiming to educate physiologists, arrhythmia nurses and physicians undertaking the Heart Rhythm UK (HRUK) certificate of accreditation examination in 2012. The HR (UK) accreditation is steadily growing in popularity year by year and this course has now firmly established itself in the annual meeting calendar.

An entire day of sessions was specifically devoted to the education of allied health professionals, including a comprehensive round-up of medical advances and updates over the last 12 months. The Primary Cardiovascular Care Society hosted an all-day programme entitled ‘A brave new world- will the NHS reforms really change the landscape?’ – a series of interesting and thought-provoking sessions exploring innovation and change across the NHS in service provision for various heart rhythm conditions. The first day of the conference was once again ‘Patient’s Day’, with meetings arranged by the Arrhythmia Alliance, Atrial Fibrillation Association and STARS (Syncope Trust And Reflex anoxic Seizures). Eminent speakers from across the UK participated in interactive educational sessions to inform and educate patients on AF, syncope and other heart rhythm problems and answer common questions. The exhibition at HRC 2011 offered an opportunity for industry sponsors to exhibit and explain some of the latest technology that is available to support health care professionals in managing patients with heart rhythm problems. Earlier this year the Department of Health published a review of emerging technologies and their potential impact on cardiac services over the next 10 years. This year’s HRC provided a fantastic opportunity for all health professionals, including those with a managerial role within the health service, to see and understand cutting-edge technology that is currently available and in development.

Research and Collaboration

Research and innovation featured once again quite highly on the agenda as in previous years. Throughout the conference there was also the opportunity for researchers to showcase the results of their work through moderated posters and oral presentations. All abstracts selected for HRC 2011 will be published in Europace, Volume 13, Supplement 4. The Young Investigators Competition included six oral presentations by young researchers from across the UK and the winners were selected by an expert panel of four judges. The winners were as follows:

Clinical: W.B. Nicholson, University of Leicester, ‘Novel Restitution Gradient Based Predictor of Ventricular Arrhythmia’.

Basic Science: G.M. Morris, University of Manchester, ‘The Funny Current can be used to Create a Biological Pacemaker by Enhancement of the Pacing Rate of Subsidiary Pacemaker Tissue in a Model of Sick Sinus Syndrome, but the Effectiveness of Different HCN Isoforms Markedly Differs’.

In addition several innovative and potentially ground-breaking technological products, at various stages of development, were displayed by exhibitors from the industry.  These offered interesting insights into the future of heart rhythm care. In the current era of austerity and rising healthcare costs, collaboration between primary, secondary and tertiary care and among different professionals at each level is vital to ensure that patient care continues to improve despite these challenges. It was therefore very encouraging to see a large turnout of allied heath professionals and primary care physicians at the meeting. There were several light-hearted moments too throughout the meeting – such as the entertaining ‘quiz competition’ between the team of GPs vs. cardiologists hosted by the PCCS, which was won by the GPs for the second year running.

The annual Gala Dinner provided yet another focal point for socialising, attended by around 450 delegates. Highlights of the Gala dinner included engrossing speeches by Dr Steve Furniss, current President of HRUK and Prof. A. John Camm on behalf of the Arrhythmia Alliance, as well as the presentation by Trudie Lobban MBE of the Arrhythmia Alliance Excellence in Practice Awards – in recognition of outstanding achievements and contributions to arrhythmia management services. The winners in 2011 were as follows:

• Award for Outstanding Medical Contribution to Cardiac Rhythm Management Services:  Jayne Mudd, Arrhythmia Nurse; James Cook Hospital, Middlesbrough, UK

• Allied Professional Award for Outstanding Contribution to Arrhythmia Management:  Jean Maloney, Arrhythmia Nurse Specialist, Sheffield Teaching Hospitals Foundation Trust

• Charles Lobban Volunteer Award for Outstanding Contribution to Arrhythmia Services: Anita Kiernan, STARS Volunteer

• Team of the Year: Dorset Cardiac and Stroke Network: Stroke Prevention & Public Awareness Subgroup and the Arrhythmia Subgroup

Updates on specific topics

Atrial fibrillation: prevention of thromboembolic events:

Perhaps the most widely discussed topic at the conference was the role of the newer oral anticoagulants, in particular dabigatran. While the decision of the National Institute for Health and Clinical Excellence (NICE) on the use of dabigatran in AF is not expected until the end of the year, experts debated in several forums the advantages and limitations of the newer anticoagulants vis-à-vis warfarin. One such interesting and entertaining session was a ‘Dragons Den’ style pitch in front of two ‘connoisseurs’ in the field of AF: Professor AJ Camm and Dr D Jenkinson, chaired by well-known TV/radio broadcaster Sue Lawley OBE. While these drugs are undoubtedly promising with some advantages over warfarin, the lack of long-term follow-up beyond 2-3 years, concerns over the absence of an antidote to reverse its effects in the event of life-threatening bleeds, contraindication in patients with eGFR <30 ml/min and cost are some of the limitations. There is also emerging data from post-hoc analyses of clinical trials that the superiority of these newer drugs over warfarin may be limited to those patients on warfarin with time in therapeutic range of <60%. Finally data from the GRASP-AF survey of primary care in the UK shows that warfarin prescription for AF is still inadequate and under-utilised in eligible patients (in line with the rest of the world) and we need to overcome challenges in identifying patients and initiating appropriate anticoagulation for AF in both primary and secondary care settings.

An alternative approach to stroke prevention in AF is the use of left atrial appendage (LAA) closure devices – a fascinating novel technological advancement over the last couple of years. The largest to date published randomised study (PROTECT-AF) enrolled just over 700 patients and concluded that LAA occlusion was non-inferior to warfarin after average follow-up of 18 months but with a higher initial safety event rate due to the procedure-related adverse events (stroke and pericardial effusion). In the absence of any UK-wide guidance on who should be considered for LAA appendage closure devices, current consensus appears to be that their use should be considered only in those with absolute contra-indications to oral anticoagulant use (e.g. oesophageal varices) and those with life-threatening bleeds (e.g. intracranial haemorrhage) while on oral anticoagulants. The implantation of these devices has steadily grown over the last 12 months. At the HRC, experts shared their experiences of LAA appendage closure with the two commercially available devices: the Watchman device and Amplatzer plug; with video demonstrations of cases to show implant techniques and pitfalls to avoid. Many speakers reiterated the importance of appropriate case selection and pre-operative imaging of the LAA with transoesophageal echocardiography (TOE) – given the variations in size and shape of LAA. Finally all speakers echoed the importance of a multi-disciplinary team collaboration (including cardiologists with imaging expertise and anaesthetists) during the procedure and the need for appropriate local clinical governance arrangements when setting up this service.

Electrophysiology:

In addition to usual trainee favourites such as interpretation of challenging electrophysiology (EP) traces, ablation for AF and ventricular tachycardia featured widely throughout the conference, in addition to focussed sessions on paediatric EP and novel ablation technologies. While there continue to be a growing number of small studies – both observational and randomised trials – reporting benefits of AF ablation in both paroxysmal and persistent AF, success rates and determinants of success remain variable and data from large clinical trials are still awaited. Ablation continues to play a small but significant role in symptomatic patients in whom anti-arrhythmic drugs are either ineffective or poorly tolerated. In one of the sessions on ‘Innovations on cardiac rhythm management’, Dr Mark O’Neill summarised succinctly the limited published evidence favouring the two opposing strategies of ablation for AF vs. ‘pace and ablate’ strategy in heart failure patients. While there is some evidence to support that the former strategy may result in improvements in LV ejection fraction during follow-up of up to 12 months, these benefits are limited to those in whom sinus rhythm is maintained and therefore careful consideration must be given to the likelihood of procedural success. On the other hand patients with persistent AF receiving cardiac resynchronisation strategy often require AV nodal ablation to achieve >90% bi-ventricular pacing necessary for maximal benefit to patients. A number of case studies of ablation for AF were also presented by experienced consultants highlighting ‘red flags’ to avoid/reduce the likelihood of complications as well as how to deal with rare but serious complications to ensure favourable patient outcomes.

One of the particular highlights of this year’s congress was two entire sessions (and six eminent speakers) dedicated to discuss ventricular tachycardia (VT) in structural heart disease, covering topics such as indications and programming of ICD, role of anti-arrhythmic therapy and role of ablation. One of the inevitable consequences of an ageing population with structural heart disease and widespread use of ICDs among these patients is the need to manage recurrent VT in these patients and this requires a holistic and multidisciplinary approach. In addition to addressing all reversible factors like ischaemia and initiating appropriate anti-arrhythmic drugs (primarily beta-blockers ± amiodarone), there is now an established role for VT ablation as an important adjunctive management strategy in selected patients such as patients with electrical storm unrelated to any reversible factors. Dr J Bourke described the contemporary role of VT ablation in structural heart disease as similar to where AF ablation was a few years ago and VT ablation numbers will grow significantly in the coming decade, thanks to encouraging short and medium-term results from centres worldwide and aided by ongoing advances in mapping and ablation technology.

Device therapy:

There continues to be a progressive increase in the implantation of cardiac resynchronisation therapy (CRT) and implantable defibrillator (ICD) devices worldwide. Despite the increase in numbers seen in UK in recent years, we still lag behind many European countries and HRUK remains committed to training both cardiologists and physiologists in the implantation and follow-up of these patients. A number of sessions focussed on updates regarding evidence to minimise inappropriate shocks from ICDs and maximise benefits from CRT devices. Professor Michael Gold from Charleston, USA gave an eloquent presentation summarising strategies to minimise inappropriate shocks by appropriate ICD programming – routine use of anti-tachycadia pacing (ATP) prior to shocks, longer detect duration for VT and use of appropriate supraventricular tachycardia (SVT) discriminators. He also presented some interesting results from his research group on the relative efficacy of various devices including the Cameron Health subcutaneous ICD on detection of VT and discrimination from SVTs. Other sessions discussed potential factors contributing to lack of benefit from CRT, which may relate to the patient (coexisting comorbidities, RV dysfunction), implantation (LV lead position, presence of LV scar) or programming (sub-optimal AV timing, <90% biventricular pacing), although reasons remain unexplained in some patients. Yet another excellent session entitled: ‘What to do when the battery runs down’ discussed four clinical dilemmas encountered increasingly frequently by device specialists when devices reach end of life; with a review of the limited published evidence currently available to guide best practice.

Device therapy continues to evolve and diversify with the industry developing novel technologies to meet the expanding needs of patients. For example magnetic resonance imaging (MRI) compatible pacemaker systems are now more widely available and MRI-compatible defibrillator systems are in development. Another such innovation that featured prominently at the conference was the availability of remote monitoring for all pacing and defibrillator devices, now offered by most manufacturers. Remote monitoring offers significant benefits to both patients and physicians. Dr J Wright presented their in-house experience of using such technology with excellent results. Benefits include not only quicker identification of potential device issues and prompt reassurance for patients if concerns but also potential cost saving once adopted by a sizeable cohort of patients. In the years to come, data from larger patient cohorts will hopefully provide more robust evidence to support the rapid uptake of this technology across all hospitals in the UK.

The problems of faulty technology were also discussed.  Malfunctioning ICD leads – though not a very frequent occurrence – continue to create difficulties for physicians and are a highly emotive subject for patients, with potentially serious adverse consequences such as inappropriate shocks and the withholding of appropriate therapy. Management of patients with faulty ICD leads was discussed extensively with emphasis on early recognition of the problem using programmable alerts and remote monitoring, and then tailoring further management to the individual patient. Other sessions focussed on strategies to minimise complications such as haematomas and infections during device implants, as these can have serious adverse consequences. Many experts agreed that, to minimise bleeding and haematomas in high risk patients where anticoagulant therapy cannot be interrupted (e.g. prosthetic metallic valves), anecdotal evidence strongly favoured the continuation of warfarin therapy with international normalised ratio (INR) no more than three rather than the use of bridging therapy with heparin or low molecular weight heparin (LMWH), although published evidence on this topic is still limited. Simple measures such as maintaining strict asepsis and performing implants in a theatre environment are also important to minimise infection. HRUK are strongly advocating robust audit data collection from all implanting centres across the UK via the Central Cardiac Audit Database (CCAD), as data is currently patchy.

Syncope and sudden cardiac death:

Since the publication of the NICE guidance on transient loss of consciousness (TLoC), there has been keen interest in setting up of TLoC clinics – as a one-stop opportunity to offer a comprehensive evaluation by a multidisciplinary team of health professionals with expertise in cardiac syncope and epilepsy. At the HRC, a series of sessions covered comprehensively the spectrum of topics on this subject spread over two days. The first afternoon focussed on the evaluation of patients with TLoC with perspectives from a range of specialities: primary care, Emergency department, cardiology, neurology and elderly care experts. The second day focussed on setting up services to effectively manage patients with TLoC. The common theme that emerged was the importance of collaboration between different specialities and need for locally agreed patient pathways to match the varied aspirations of health professionals, managers and patients. Evidence from multidisciplinary clinics set up in recent years appears to suggest that this approach not only leads to swift and accurate diagnosis, but is also cost-effective and has elicited good feedback from patients. In association with STARS, a dedicated website has been designed to support the set-up and management of a triage tool for new TLoC clinics; the website is www.starsloc.org.

The HRC provided an opportunity for physicians to update their knowledge on inherited heart conditions that are seen less frequently but can have potentially serious consequences for patients, including sudden cardiac death. Every year the number of confirmed cases is increasing, identified by three distinct strategies: identification of disease phenotype in new index cases, phenotypical disease identified by cascade familial screening and asymptomatic first-degree relatives of patients identified by genetic screening. Most cardiac networks have a hub-and-spoke model with specialist inherited cardiac conditions clinics that comprise of health professionals with expertise in both cardiology and genetics. World-renowned experts provided updates on when to consider defibrillators in the four common inherited conditions: hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy (ARVC), long QT syndrome and Brugada syndrome. There is general consensus that patients with cardiac arrest or symptomatic ventricular arrhythmias should be offered ICDs for secondary prevention. However prophylactic ICD implantation remains controversial in low-to-intermediate risk patients, especially given the lifetime risk of lead extraction / redo procedures and inappropriate shocks in young patients. All speakers emphasised the absence of a large body of evidence for risk stratification in asymptomatic and minimally symptomatic patients and the changing patient demographics and risk profile in these conditions. Dr Perry Elliott who spoke on hypertrophic cardiomyopathy stressed the importance of taking into account the patient’s age and progression of disease while weighing up risk factors to consider a prophylactic ICD implant e.g. spontaneous non-sustained VT on Holter is an important risk factor in young individuals but is perhaps less significant in older patients or patients with co-existing coronary artery disease (CAD). Decision making regarding ICD implantation needs to be individualised after a frank discussion with the patients about the risks and uncertainties regarding benefit.

On the whole HRC 2011 was once again of immense educational value to all delegates, providing comprehensive updates from world-renowned experts and showcasing the latest in research and innovation, while at the same time being an enjoyable event – offering something for everyone. HRC 2012 will be held from 23^rd – 26^th September at The ICC, Birmingham UK; further details will be available in due course on the website www.heartrhythmcongress.com.

Author

Dr Karthik Viswanathan, Specialist registrar (EP and devices), Leeds General Infirmary, West Yorkshire

Dr Karthik Viswanathan

In the CD cohort 941 individuals developed AF during a median follow-up of nine years, compared to 2,918 reference individuals. The corresponding adjusted hazard ratio for AF was 1.34, and the absolute risk of AF in CD was 321 of 100,000 person-years, with an excess risk of 81 of 100,000.  A prior AF diagnosis was also associated with an increased risk of subsequent CD.

Possible explanations for the increased risk of AF include chronic inflammation and shared risk factors, although ascertainment bias may also have contributed, say the authors.  They assert that “patients with coeliac disease, verified by intestinal biopsy, are at increased risk of atrial fibrillation…Additional studies are needed to clarify the mechanistic link between atrial fibrillation and autoimmune diseases such as coeliac disease”.

Professor Jonas F Ludvigsson

Senior author, Professor Jonas F Ludvigsson (Örebro University Hospital, Sweden), told Arrhythmia Watch: “Although we believe that coeliac disease is associated with an excess risk of atrial fibrillation we do not suggest mandatory cardiovascular screening [for AF].

“But I think that our findings illustrate that inflammation/autoimmune disease may increase the risk of AF…in patients with CD it is reasonable to have an increased awareness of symptoms that might indicate AF,” he added.

References

1 Emilsson L, Smith JG, West J, Melander O, Ludvigsson JF.  Increased risk of atrial fibrillation in patients with coeliac disease: a nationwide cohort study.  Eur Heart J 2011 (online).  doi: 10.1093/eurheartj/ehr167

PubMED, PsycINFO, EMBASE and CINAHL databaageses were searched using pre-determined search terms during May 2011. Thirty-three articles meeting inclusion criteria were subsequently included in the review. Findings revealed that anxiety and depression are common post-implantation with rates of up to 60% and 40%, respectively, reported by the literature. The influence of additional factors including time since implantation and receipt of shocks was also investigated, however, whether there is any association between these factors remains unclear.

The findings reported by this review are limited by the fact that there are gross inconsistencies in the literature in terms of the methodology employed and the time elapsed since implantation. Future research should be carried out prospectively and assess participants pre- and post-implantation.

Introduction

The implantable cardioverter defibrillator (ICD) is the recommended treatment for life-threatening ventricular arrhythmias.¹ By identifying potentially fatal arrhythmias and administering therapeutic electrical shocks the ICD substantially reduces the risk of sudden cardiac death. ^2,3 However, the ICD is associated with a multitude of psychosocial issues⁴ which can adversely affect the prognosis of coronary heart disease (CHD), such as depression^4,5 and anxiety disorders,^4-6 including panic attacks.⁵

The present paper seeks to examine the prevalence of psychopathology amongst people with ICDs. Specifically, this paper will: (1) examine the prevalence of anxiety and depression among adults (>18 years) receiving ICDs; (2) identify personal (age, gender) and clinical (diagnosis) factors associated with the experience of anxiety or depression among people with ICDs.

Methods

The current review considered studies of adults receiving ICDs for the primary or secondary prevention of sudden cardiac death.  Articles for inclusion (1985-2011) were identified in May 2011 by searching PubMED, PsycINFO, EMBASE and CINAHL databases using the following terms: implantable cardioverter defibrillator, anxiety, depression, depressive disorder, deprsudessive symptoms, quality of life, psychopathology, distress, emotional factors, psychosocial factors, symptom distress, mental health.  Reference lists from selected articles were examined and key authors contacted to identify relevant studies and recently published or “in press” journal articles.

Inclusion criteria:

• Address issues of anxiety and depression
• Use either structured/semi-structured interviews or standardised measures to assess anxiety and depression
• Include participants of both genders, over the age of 18
• Employ primary data
• Reported in the English language.

Data extraction forms were used to summarise the characteristics of these studies and their results.   Studies were classified according to SIGN⁷ (table 1).

Table 1. Classification of studies based on levels of evidence

The methodological quality of these studies was scrutinised using checklists from SIGN/CASP,^7,8 adapted for the purposes of this review.  The studies were then given an overall rating (table 2).

Table 2. Criteria for overall assessment of studies

Any uncertainty relating to the inclusion of articles was discussed with the second author.  In the case of multiple articles using the same sample, employing the same assessment methods within the same period of time, only the study with the largest sample size was included.

Results

Using the outlined search terms 2,739 studies were identified.  Thirty-three studies were subsequently included in the review (figure 1).

Figure 1. Flow chart of review process

Study characteristics

The overall sample size for the included studies was 4,501 (range 20-610).   The mean participant age was 62.4 years.  Seventy-seven percent of participants were male (table 3).

Table 3. Study assessment

A variety of assessment methods were used by the studies, including the Hospital Anxiety and Depression Scale (HADS), the State Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and the Centre for Epidemiological Studies-Depression Scale (CES-D).  In addition, a number of studies employed structured or semi-structured interviews.

Seven studies recruited participants prior to the receipt of their device.  Of the remaining studies, the duration from implant to study participation varied from one day to 88 months.  Follow-up assessment ranging from one month to two and a half years featured in 17 studies.  Eight studies included more than one follow-up.

Anxiety

The prevalence of anxiety ranged from 5.8 to 62.8% dependent on when the assessment took place and the method employed.^9,10 Pre-implant levels of anxiety measured in the days prior to receipt of the device ranged from 34% to 62.8%.^10-16 The six studies assessing participants within three-months of implantation noted that between 5.8% and 48% may experience anxiety.^9,15,17-20 The remaining studies, which addressed anxiety at least one year post-implant found that between 13% and 41% scored above the cut-off points suggestive of caseness.^21-25 One study²⁶ with a period of 88 months from implantation to recruitment found that 34.9% scored above the cut-off points on the STAI.  The six studies which included follow-up periods^10,12,26-28 suggest some stability in prevalence of post-implantation anxiety throughout five years of follow-up.^10,20,26,27

Assessment of panic disorder (PD) within days of placement identified a prevalence of 5.9%.⁹ Similar prevalence rates of 5% were noted at seven and a half months post-implant.²⁹ However, estimates were comparatively higher (19.4%) among recipients at three and a half years post-implant.³⁰ The assessment of PD as detailed by these studies was carried out using structured/semi-structured interviews, including the SCID and DIPS.^31,32

There has been some consideration of the correlation of post-implantation anxiety and patient characteristics.  For example, significantly higher anxiety scores have been noted among female recipients (6) and amongst individuals who smoke and use psychotropic medication.¹⁷ Age has been both negatively and positively correlated with anxiety amongst this population.^21,28,30

Features of the device implantation may be implicated in the prevalence of anxiety.  Three studies^22,25,33 investigated the relationship between time since implant and anxiety.  However, although one study³³ suggested anxiety decreases over time, two studies^22,25 reported no such relationship.  It has been suggested the severity of post-implant physical symptoms associated with heart failure, as classified by the New York Heart Association, may be associated with anxiety.³⁴

Patients fulfilling criteria for an anxiety disorder are often preoccupied with anxiogenic predictions of imminent ICD firing, fear of device malfunction, death, feelings of loss of control ³⁴ and, as such, constantly self-monitor for signs of an impending shock (30).  Additionally, high scores on the Anxiety Severity Index were related to the perceived predictability of a shock, interference of activities due to worrying about shock, and time spent worrying about shock.²⁷

Depression

The prevalence of depression ranged from 5-38%.^12,15,19 Six studies examining the prevalence of depression prior to ICD placement^10-14,16 reported pre-implant prevalence of 23-35.8%^11,14 with an estimate that 20.8% had mild, 5.7% moderate, and 9.4% severe depression.¹⁴

The prevalence of depression was assessed at varying time-points post-implantation with estimates ranging from 5-38%.^21,35 Within three-months of implantation, the prevalence of depression varied from 11-20%.^9,16,20 At approximately seven and a half months post-implant 15% experienced major depression.²⁹ The remaining studies, monitoring depression at least one-year post-implant, reported prevalence between 5% and 38%.^{22-25,27,35-38}

Six studies addressing the prevalence of depression featured more than one follow-up period^{9,10,12,19,20,27} ranging from one-month^10,19 to two years post-implant^9,12,20,27 with a maximum of four follow-ups.^10,19 The reviewed studies suggest depression amongst recipients of ICDs is a stable trait.^{9,10,12,19,20,27} Neither of two prospective studies noted a significant difference in the prevalence of depression at pre- and post-implantation.^10,12

The specific presence of major depressive disorder was examined by two of the included studies and ranged from 8.6% to 15%.^9,29 At nine to eighteen months follow-up one of these studies noted that 7.4% could be classified as having major depressive disorder.⁹

Post-implant depression has been linked to patient characteristics.  For example, women were reported to be more likely to experience depression.²⁵ Persistent depression was suggested to be associated with older age by one study.¹⁶ However, similar research suggests that age may be negatively correlated with depression.²¹ Marital status and highest level of education are also suggested to be associated with depression among this population.²⁴ Additional factors associated with depression include poor social support and poor physical functioning.²⁴

Iatrogenic factors inherent in the ICD may increase the likelihood of depression including the receipt of one or more shocks,²⁴ as well as fear of ICD firing.²⁷ Clinical factors such as having CRT, heart failure, in particular NYHA classes III/IV, and previous CABG, in addition to the use of diuretics and psychotropic medicines are suggested to be associated with persistent depression, type D behaviour pattern and high ICD concerns within this population.¹⁶ Time since implant may significantly predict depression independent of ejection fraction status,^24,33 with significant differences in depression based on follow-up lowest in one to five years, but increasing thereafter.⁶ However, such an influence is not universally reported.²⁵

Shocks

The administration of therapeutic shocks for the correction of potentially fatal arrhythmias occurs in 4.2 to 90% of ICD recipients.^16,17,29 However, such figures may be influenced by time since implantation.³⁹ When the population prevalence of shock for the overall sample of studies was calculated, this was approximately 29%.  The number of shocks received by an individual ranged from one to over ten, with one study³⁷ reporting that 17.1% had received upwards of ten shocks.  Shock storms, typically classed as three or more shocks within a 24 hour period, were reported by five studies and were experienced by 2.2% to 11% of ICD recipients.^{15,16,20,22,36}

It has been purported that ICD shocks²⁵ and the number of shocks received^28,40 may be correlates of psychological distress.  Nineteen studies investigated the relationship between shocks and distress with one study²⁰ noting that almost two-thirds of participants experiencing shocks had clinical anxiety.  Further, individuals with a specific anxiety disorder have been shown to experience significantly more shocks per year compared to their non-anxious counterparts.³⁰ Time since implantation could be influential in determining emotional reaction.  For example, ICD recipients shocked within a year post-implantation are more likely to experience anxiety at one-year follow-up compared to their non-shocked peers.¹⁰ The receipt of shocks likely leads to concerns about the device,¹⁷ and corresponding anxiety related to shocks as displayed in one-third of recipients.³⁹

The receipt of just one shock may be sufficient to cause a person to experience symptoms akin to depression.³⁸ Furthermore, people experiencing two or more shocks within a month have been suggested to be significantly more depressed than those receiving less than four a year.⁶ The number of shocks received and duration since last shock are significantly associated with depression in a positive and negative direction respectively.⁶ However, recent research has suggested that shock was not associated with depression^16,19,36 nor anxiety.^19,36

Discussion

The ICD is a life-saving device with the ability to reduce the occurrence of potentially fatal arrhythmias.  Nevertheless, it has been speculated that the ICD and its therapeutic mode is associated with poor psychosocial outcomes.  The present review sought to clarify the nature of the relationship between the ICD and the experience of shocks with psychological distress.

The existing literature reveals confusing and often contradictory conclusions regarding the true extent of psychological difficulties associated with ICD implantation.  It appears a high proportion of people with ICDs display some form of psychopathology post-implantation.  Both anxiety and depression appear to be common post-implantation with estimates of up to two-thirds, and two-fifths of patients, respectively, experiencing such problems and research suggesting significant chronicity of such difficulties.^{9,10,19,20,27} However, the paucity of prospective studies available limits the extent to which it can be determined whether the ICD and its associated shocks cause these adverse outcomes.  Based on the available research it is not possible to confidently conclude whether people receiving shocks are at an increased risk of developing anxiety or depression, or whether such difficulties are directly due to their ICD firing.  Any confidence in the literature is confounded by the adoption of multifarious methodology including study design, time of recruitment and assessment, assessment measures utilised, and criteria used.

The current paper aimed to identify factors associated with the prevalence of anxiety and depression in post-implant ICD patients.  It has been suggested that gender and age may influence the development of psychopathology, which is not unreasonable due to the stress, limitations in activities of daily living and socialisation experienced by many.⁴¹ Additionally, among younger recipients maladjustment to the device may be related to body image issues occurring as a result of scarring, or concerns about childbearing.^19,42 Furthermore, fear and worry about the device, and the implications that a device shock may have for oneself or another are noted to be the most distressing aspects of treatment for many.³⁹ However, no clear conclusions can be drawn regarding whether factors such as gender, age or time since implant have an impact on the subsequent development of psychopathology.  Similarly, although the association between the experience of shocks and anxiety and depression was mostly positively correlated, contradictory findings were reported.^19,36 Based on the included studies it is not possible to confidently limn the factors that increase the likelihood of experiencing either anxiety or depression as a result of ICD firing.

The number of shocks experienced by participants varied significantly between studies yet the reason underlying this is not clear.  For example, demographic and clinical factors were often not accounted for within the statistical analyses.  A limited amount of research suggests that emotional factors such as anger, mental stress and anxiety may influence the occurrence of arrhythmias and subsequent ICD firing.^43-46 However, although intriguing, this remains a tentative suggestion since such factors were not sufficiently addressed by the included studies to permit the declaration of a meaningful conclusion in this regard.

Recommendations

Recognition of the high prevalence of emotional distress amongst people with ICDs supports previous recommendations of the need for patients’ care by multidisciplinary teams to be psychologically informed including the availability of access to specialist psychological services for appropriate assessment and management.⁵ This could include the provision of pre-implantation assessment to help identify the presence of any ICD-related misconceptions likely to affect subsequent adjustment to the device and provide an opportunity for patients to discuss any concerns or distress.  There is increasing evidence that such cognitively oriented interventions have value within the ICD population enhancing patient wellbeing and leading to minimising use of healthcare resources.¹²

The variety of research methods used within this area precludes the assimilation of data, the ability to meaningfully compare studies, and assert findings with confidence.  For example, the majority of the reviewed studies examining the relationship between certain emotional states and ICD firing used a retrospective design and thus limit any confidence in the findings of these investigations.  Prospective studies, recruiting patients prior to the receipt of the device, would allow patient levels of anxiety pre- and post-implantation, to be monitored and control for other potentially confounding variables.  The identification of such factors would allow for the development of interventions to specifically target and improve the psychological well-being of such vulnerable populations.

Summary

The present paper presents a description of the literature investigating the prevalence of psychological difficulties following ICD implantation.

Conflict of interest

None declared.

Key messages

• ICDs are associated with a multitude of psychosocial issues, many of which are a result of ICD placement and subsequent firing.
• ICD shocks and number of shocks received may be correlates of psychological distress.
• It is unclear whether factors such as time since implant have an impact on the development of anxiety or depression post-implantation.
• Patients should be assessed pre- and post-implantation, which may assist subsequent adjustment to the device.

References

1. National Institute of Clinical Excellence. Implantable cardioverter defibrillators (ICDs) for the treatment of arrhythmias. 2006;TA95.
2. Nanthakumar K, Epstein AE, Kay GN, Plumb VJ, Lee DS. Prophylactic implantable cardioverter-defibrillator therapy in patients with left ventricular systolic dysfunction: a pooled analysis of 10 primary prevention trials. J Am Coll Cardiol 2004 Dec 7;44(11):2166-72.
3. Connolly SJ, Gent M, Roberts RS, Dorian P, Roy D, Sheldon RS, et al. Canadian implantable defibrillator study (CIDS) : a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation 2000 Mar 21;101(11):1297-302.
4. Dunbar SB. Psychosocial issues of patients with implantable cardioverter defibrillators. Am J Crit Care 2005 Jul;14(4):294-303.
5. Sears SF,Jr, Conti JB, Curtis AB, Saia TL, Foote R, Wen F. Affective distress and implantable cardioverter defibrillators: cases for psychological and behavioral interventions. Pacing Clin Electrophysiol 1999 Dec;22(12):1831-4.
6. Bilge AK, Ozben B, Demircan S, Cinar M, Yilmaz E, Adalet K. Depression and anxiety status of patients with implantable cardioverter defibrillator and precipitating factors. Pacing Clin Electrophysiol 2006 Jun;29(6):619-26.
7. Scottish Intercollegiate Guidelines Network (SIGN). Critical Appraisal: Notes and Checklists. Available at: http://www.sign.ac.uk/methodology/checklists.html. Accessed 19/04, 2011.
8. Critical Appraisal Skills Programme. 12 questions to help you make sense of cohort study. . Accessed 19/04, 2011.
9. Crow SJ, Collins J, Justic M, Goetz R, Adler S. Psychopathology following cardioverter defibrillator implantation. Psychosomatics 1998 Jul-Aug;39(4):305-10.
10. Kamphuis HC, de Leeuw JR, Derksen R, Hauer RN, Winnubst JA. Implantable cardioverter defibrillator recipients: quality of life in recipients with and without ICD shock delivery: a prospective study. Europace 2003 Oct;5(4):381-9.
11. Smith G, Dunbar SB, Valderrama AL, Viswanathan B. Gender differences in implantable cardioverter-defibrillator patients at the time of insertion. Prog Cardiovasc Nurs 2006 Spring;21(2):76-82.
12. Lewin RJ, Coulton S, Frizelle DJ, Kaye G, Cox H. A brief cognitive behavioural preimplantation and rehabilitation programme for patients receiving an implantable cardioverter-defibrillator improves physical health and reduces psychological morbidity and unplanned readmissions. Heart 2009 Jan;95(1):63-9.
13. Fritzsche K, Forster F, Schweickhardt A, Kanwischer H, Drinkmann A, Rabung S, et al. Depressive coping is a predictor for emotional distress and poor quality of life in a German-Austrian sample of cardioverter-defibrillator implant recipients at 3 months and 1 year after implantation. Gen Hosp Psychiatry 2007 Nov-Dec;29(6):526-36.
14. Thomas SA, Friedmann E, Gottlieb SS, Liu F, Morton PG, Chapa DW, et al. Changes in psychosocial distress in outpatients with heart failure with implantable cardioverter defibrillators. Heart & Lung: The Journal of Acute and Critical Care 2009 4;38(2):109-20.
15. Irvine J, Firestone J, Ong L, Cribbie R, Dorian P, Harris L, et al. A Randomized Controlled Trial of Cognitive Behavior Therapy Tailored to Psychological Adaptation to an Implantable Cardioverter Defibrillator. Psychosomatic Medicine 2011 April 01;73(3):226-33.
16. Pedersen SS, den Broek KC, Theuns DA, Erdman RA, Alings M, Meijer A, et al. Risk of chronic anxiety in implantable defibrillator patients: A multi-center study. Int J Cardiol 2011 Mar 17;147(3):420-3.
17. van den Broek KC, Nyklicek I, Denollet J. Anxiety predicts poor perceived health in patients with an implantable defibrillator. Psychosomatics 2009 Sep-Oct;50(5):483-92.
18. Van den Broek KC, Nyklicek I, Van der Voort PH, Alings M, Denollet J. Shocks, personality, and anxiety in patients with an implantable defibrillator. Pacing Clin Electrophysiol 2008 Jul;31(7):850-7.
19. Dunbar SB, Langberg JJ, Reilly CM, Viswanathan B, McCarty F, Culler SD, et al. Effect of a psychoeducational intervention on depression, anxiety, and health resource use in implantable cardioverter defibrillator patients. Pacing Clin Electrophysiol 2009 Oct;32(10):1259-71.
20. Kapa S, Rotondi-Trevisan D, Mariano Z, Aves T, Irvine J, Dorian P, et al. Psychopathology in Patients with ICDs over Time: Results of a Prospective Study. Pacing Clin Electrophysiol 2009 Nov 18.
21. Friedmann E, Thomas SA, Inguito P, Kao CW, Metcalf M, Kelley FJ, et al. Quality of life and psychological status of patients with implantable cardioverter defibrillators. J Interv Card Electrophysiol 2006 Oct;17(1):65-72.
22. Newall EG, Lever NA, Prasad S, Hornabrook C, Larsen PD. Psychological implications of ICD implantation in a New Zealand population. Europace 2007 Jan;9(1):20-4.
23. Leosdottir M, Sigurdsson E, Reimarsdottir G, Gottskalksson G, Torfason B, Vigfusdottir M, et al. Health-related quality of life of patients with implantable cardioverter defibrillators compared with that of pacemaker recipients. Europace 2006 Mar;8(3):168-74.
24. Luyster FS, Hughes JW, Waechter D, Josephson R. Resource loss predicts depression and anxiety among patients treated with an implantable cardioverter defibrillator. Psychosom Med 2006 Sep-Oct;68(5):794-800.
25. Johansen JB, Pedersen SS, Spindler H, Andersen K, Nielsen JC, Mortensen PT. Symptomatic heart failure is the most important clinical correlate of impaired quality of life, anxiety, and depression in implantable cardioverter-defibrillator patients: a single-centre, cross-sectional study in 610 patients. Europace 2008 May;10(5):545-51.
26. Crossmann A, Pauli P, Dengler W, Kuhlkamp V, Wiedemann G. Stability and cause of anxiety in patients with an implantable cardioverter-defibrillator: a longitudinal two-year follow-up. Heart Lung 2007 Mar-Apr;36(2):87-95.
27. Hegel MT, Griegel LE, Black C, Goulden L, Ozahowski T. Anxiety and depression in patients receiving implanted cardioverter-defibrillators: a longitudinal investigation. Int J Psychiatry Med 1997;27(1):57-69.
28. Luderitz B, Jung W, Deister A, Marneros A, Manz M. Patient acceptance of the implantable cardioverter defibrillator in ventricular tachyarrhythmias. Pacing Clin Electrophysiol 1993 Sep;16(9):1815-21.
29. Morris PL, Badger J, Chmielewski C, Berger E, Goldberg RJ. Psychiatric morbidity following implantation of the automatic implantable cardioverter defibrillator. Psychosomatics 1991 Winter;32(1):58-64.
30. Godemann F, Ahrens B, Behrens S, Berthold R, Gandor C, Lampe F, et al. Classic conditioning and dysfunctional cognitions in patients with panic disorder and agoraphobia treated with an implantable cardioverter/defibrillator. Psychosom Med 2001 Mar-Apr;63(2):231-8.
31. Margraf J, editor. Diagnostic Interview of Psychiatric Disease (DIPS). Berlin; 1994.
32. Spitzer R, Williams J, Gibbon M, et al. Structured Clinical Interview for DSM-III-R Patient Version (SCID-P). 1988.
33. Wheeler EC, Pretzer-Aboff I, Hardie T, Disabatino A, Saylor J, Lucey R. Psychological impact of implantable cardioverter defibrillator on their recipients. Dimens Crit Care Nurs 2009 Jul-Aug;28(4):176-81.
34. Schuster PM, Phillips S, Dillon DL, Tomich PL. The psychosocial and physiological experiences of patients with an implantable cardioverter defibrillator. Rehabil Nurs 1998 Jan-Feb;23(1):30-7.
35. Wallace RL, Sears SF,Jr, Lewis TS, Griffis JT, Curtis A, Conti JB. Predictors of quality of life in long-term recipients of implantable cardioverter defibrillators. J Cardiopulm Rehabil 2002 Jul-Aug;22(4):278-81.
36. Redhead AP, Turkington D, Rao S, Tynan MM, Bourke JP. Psychopathology in postinfarction patients implanted with cardioverter-defibrillators for secondary prevention. A cross-sectional, case-controlled study. J Psychosom Res 2010 12;69(6):555-63.
37. Duru F, Buchi S, Klaghofer R, Mattmann H, Sensky T, Buddeberg C, et al. How different from pacemaker patients are recipients of implantable cardioverter-defibrillators with respect to psychosocial adaptation, affective disorders, and quality of life? Heart 2001 Apr;85(4):375-9.
38. Herrmann C, von zur Muhen F, Schaumann A, Buss U, Kemper S, Wantzen C, et al. Standardized assessment of psychological well-being and quality-of-life in patients with implanted defibrillators. Pacing Clin Electrophysiol 1997 Jan;20(1 Pt 1):95-103.
39. Pauli P, Wiedemann G, Dengler W, Blaumann-Benninghoff G, Kuhlkamp V. Anxiety in patients with an automatic implantable cardioverter defibrillator: what differentiates them from panic patients? Psychosom Med 1999 Jan-Feb;61(1):69-76.
40. Herbst JH, Goodman M, Feldstein S, Reilly JM. Health-related quality-of-life assessment of patients with life-threatening ventricular arrhythmias. Pacing and Clinical Electrophysiology 1999;22(6):915-26.
41. Schron EB, Exner DV, Yao Q, Jenkins LS, Steinberg JS, Cook JR, et al. Quality of life in the antiarrhythmics versus implantable defibrillators trial: impact of therapy and influence of adverse symptoms and defibrillator shocks. Circulation 2002 Feb 5;105(5):589-94.
42. Vazquez LD, Kuhl EA, Shea JB, Kirkness A, Lemon J, Whalley D, et al. Age-specific differences in women with implantable cardioverter defibrillators: an international multi center study. Pacing Clin Electrophysiol 2008 Dec;31(12):1528-34.
43. Lampert R, Joska T, Burg MM, Batsford WP, McPherson CA, Jain D. Emotional and physical precipitants of ventricular arrhythmia. Circulation 2002 Oct 1;106(14):1800-5.
44. Fries R, König J, Schäfers H, Böhm M. Triggering effect of physical and mental stress on spontaneous ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators. Clin Cardiol 2002;25(10):474-8.
45. Kawachi I, Sparrow D, Vokonas PS, Weiss ST. Decreased heart rate variability in men with phobic anxiety (data from the normative aging study). Am J Cardiol 1995 5/1;75(14):882-5.
46. Albert CM, Chae CU, Rexrode KM, Manson JE, Kawachi I. Phobic anxiety and risk of coronary heart disease and sudden cardiac death among women. Circulation 2005 Feb 1;111(4):480-7.

Authors

Deirdre Holly, BHF Assistant Psychologist

John Sharp, BHF Principal Clinical Psychologist

Corresponding author
Deirdre Holly, BHF Assistant Psychologist, Cardiac Psychology Service, The Lister Centre, Crosshouse Hospital, Kilmarnock, KA2 0BE

Citation

Holly D, Sharp J.  The psychological impact of the implantable cardioverter defibrillator: A systematic review.  Arrhythmia Watch 2011;Issue 17 (Oct)

Conducted in 1,034 centres in 39 countries, the study was coordinated by the Duke Clinical Research Institute, Durham, N.C., and Uppsala Clinical Research Institute, Uppsala, Sweden.

“The risk for stroke in patients with AF is a major public health concern in an aging population,” said Dr. Christopher B. Granger, Professor of Medicine, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA, and lead investigator of the study. “We are therefore encouraged by the outcome of the ARISTOTLE trial, which showed that apixaban, as compared with warfarin, significantly reduced the risk of stroke or systemic embolism, major bleeding, and mortality.”

ARISTOTLE

ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation), a randomised, double-blind, multicentre, head-to-head trial, included 18,201 patients with AF and at least one additional risk factor for stroke. The mean CHADS₂ risk score for the study population was 2.1. Patients were randomised to receive either apixaban (n=9,120) 5 mg orally twice daily (2.5 mg twice daily in selected patients) or warfarin (n=9,081) dosed to achieve a target INR (International Normalised Ratio) of 2.0-3.0.

The key study outcomes were pre-specified in a hierarchical manner that sequentially tested apixaban versus warfarin for non-inferiority on the composite endpoint of stroke or systemic embolism; superiority on the composite endpoint of stroke or systemic embolism; superiority on major bleeding; and superiority on all-cause death. The efficacy analyses included all randomised patients (“intention to treat”); bleeding analyses were “on treatment” and included all randomised patients who received at least one dose of study drug. Apixaban demonstrated non-inferiority (p<0.001) for the primary efficacy outcome, composite of stroke or systemic embolism, compared with warfarin. The relative risk reduction was 21% with annual event rates of 1.27% for apixaban and 1.60% for warfarin in an intention to treat analysis. Additionally, apixaban met the key secondary objective of superiority for the primary outcome of the composite of stroke or systemic embolism (p=0.01). The predominant effect on stroke prevention was on haemorrhagic stroke, which was 49% lower with apixaban than warfarin (p<0.001), along with an effect on ischaemic or uncertain stroke that was 8% lower with apixaban than with warfarin (p=0.42, NS).

Results from ARISTOTLE also demonstrated that apixaban was superior to warfarin for the primary safety outcome of ISTH major bleeding (p<0.001), yielding a significant relative risk reduction of 31%, with annual event rates of 2.13% for apixaban and 3.09% for warfarin. Additionally, apixaban significantly reduced the risk for ISTH major or clinically relevant non-major bleeding by 32% (p<0.001) compared to warfarin. Any bleeding was reduced 29 % per year compared with warfarin (p<0.001). With apixaban, the risk for intracranial haemorrhage was significantly reduced by 58% compared with warfarin (p<0.001).

ARISTOTLE demonstrated that apixaban is the first novel oral anticoagulant to significantly reduce all-cause death compared to warfarin. For the pre-specified key secondary efficacy outcome of all-cause death, apixaban was superior to warfarin (p=0.047). Specifically, there was a statistically significant 11% relative risk reduction with apixaban compared to warfarin, with annual event rates of 3.52% and 3.94%, respectively. (Table 1)

Table 1. Apixaban versus warfarin, significantly reduced relative risk of:

• Stroke or systemic embolism by 21% (p=0.01)
• Major bleeding by 31% (p<0.001)
• All-cause mortality by 11% (p=0.047)

In ARISTOTLE, adverse events were similar in the apixaban (81.5%) and warfarin (83.1%) groups, as were serious adverse events (35.0% with apixaban and 36.5% with warfarin). Discontinuation of study drug was significantly less common with apixaban (25.3% of patients, 3.6% due to death) than with warfarin (27.5% of patients, 3.8% due to death; p=0.001). Data presented by the trial co-investigator, Professor Lars Wallentin, Uppsala Clinical Research Centre, Sweden, showed that , among patients on warfarin, time in therapeutic range (TTR) as assessed by INR (International Normalised Ratio) range of 2.0–3.0 was a median of 66.0% and mean of 62.2%, excluding INR values during the seven days following randomisation and during study drug interruptions.

Overall, safety and efficacy findings were consistent across subgroups, including geographical regions, warfarin experienced and naïve patients, age groups, sexes, differences in renal function, differences in risk for stroke, as well as in other predefined subgroups.

Apixaban

Apixaban (Eliquis) is not yet approved for the prevention of stroke or systemic embolism in patients with AF. Bristol-Myers Squibb and Pfizer recently announced the first regulatory approval for apixaban in the 27 countries of the European Union (EU) for the prevention of venous thromboembolic events (VTE) in adult patients who have undergone elective hip or knee replacement surgery.

Apixaban is being investigated within the EXPANSE Clinical Trials Programme, which is projected to include nearly 60,000 patients worldwide across multiple indications and patient populations and includes a total of nine completed or ongoing, randomised, double-blind Phase 3 trials, including ARISTOTLE. The apixaban AF clinical trial programme, which includes ARISTOTLE and AVERROES, was designed to comprehensively evaluate apixaban in approximately 24,000 patients with AF, including patients who are expected or demonstrated to be unsuitable for vitamin K antagonist (VKA) therapy.

References

1 Granger CB et al.  Apixaban versus warfarin in patients with atrial fibrillation.  N Engl J Med 2011 Aug 28; doi 10.1056/NEJMoa1107039.

Researchers led by Professor Henrik Toft Sørensen, Aarhus University Hospital, Denmark, identified 32,602 subjects in the Danish National Registry of Patients with a first diagnosis of AF or flutter between 1999 and 2008.  Each case was compared with 10 age and sex-matched control patients (n = 325,918) randomly selected from the Danish population.

Patients were classified as current or recent NSAID users. Current users were further classified as new users (first ever prescription within 60 days of diagnosis date) or long-term users.

The researchers found that use of NSAIDs or COX-2 inhibitors was associated with an increased risk of AF or flutter.

Compared with non users, the association was strongest for new users, with a 46% increased risk for non-selective NSAIDS and a 71% increased risk for COX-2 inhibitors. This is equivalent to approximately four extra cases of AF per year per 1,000 new users of non-selective NSAIDS and seven extra cases of AF per 1,000 new users of COX-2 inhibitors.

The risk appeared highest in older people, and patients with chronic kidney disease or rheumatoid arthritis were at particular risk when starting treatment with COX-2 inhibitors.

The authors conclude: “Our study thus adds evidence that AF or flutter need to be added to the cardiovascular risks under consideration when prescribing NSAIDs”.

This view is supported by an accompanying editorial² by Professor Jerry Gurwitz from the University of Massachusetts Medical School in the US. He believes that NSAIDS should continue to be used very cautiously in older patients with a history of hypertension or heart failure, regardless of whether an association between NSAIDs and AF actually exists.

Gurwitz also observes that the study found highest risk amongst new users, while the UK database study found highest risk among long-term users, both trials showing a lack of consistent dose response.  Gurwitz adds that case-control studies are subject to unmeasured confounding variables, such as obesity. In this analysis, Schmidt et al were unable to obtain data on several clinical measures, including body-mass index.

Gurwitz says: “What should clinicians do in practice in the light of current evidence?  With uncertainty regarding a plausible biological mechanism, the susceptibility of case-control studies to unmeasured confounders, and inconsistent results in the two studies performed to date, a cautious approach seems warranted in applying the study’s results to the care of patients”.

References

1 Schmidt M, Christiansen CF, Mehnert F, Rothman KJ, Sørensen HT.  Non-steroidal anti-inflammatory drug use and risk of atrial fibrillation or flutter: population based case-control study. BMJ 2011;343:d3450. doi: 10.1136/bmj.d3450.

2 Gurwitz JH. NSAIDs and atrial fibrillation. BMJ 2011;343:d2495. doi: 10.1136/bmj.d2495.

At the six-month follow-up after CRT, 23 patients reported no ED, two patients had moderate ED, and severe dysfunction was not found in any patient. A significant increase in patients with normal libido was found, with 25 men reporting improvement compared to only three reporting normal libido prior to CRT.

The authors say that the apparent benefits of CRT for libido, ED, and sexual performance are a consequence of the improvement in functional capacity and ejection fraction.  “Not only does CRT decrease mortality in heart failure patients, it also brings improvement in sexual health to the patient’s life,” Vural concludes.

****

Guha K, Sharma R. Editorial Response to Effect of Cardiac Resynchronisation Therapy on Libido and Erectile Dysfunction:

Cardiac resynchronisation therapy (CRT) is an established therapeutic option for selected patients with symptomatic left ventricular systolic dysfunction and a broad QRS complex. The cardiac benefits of CRT in this cohort are well documented with improvements in terms of both morbidity and mortality. Vural et al suggest a somewhat unexpected non-cardiac benefit from this therapy CRT.

Utilising a cohort undergoing CRT implantation, they demonstrate an improvement in erectile dysfunction and libido after six months. This was investigated using symptom score questionnaires and a validated classification system (SHIM index – Sexual Health Inventory for Men). Notably the cohort was younger (Mean Age= 54 +/- 8 ) as compared to patients enrolled in randomised controlled trials of CRT. The majority of patients had a dilated cardiomyopathy as an aetiology for their heart failure. Due to the limited number of patients, no meaningful analysis could be performed on sub groups with diabetes mellitus or hypertension.

There was a significant improvement in erectile dysfunction following CRT. Correspondingly, the symptom score questionnaire demonstrated an increase in libido and psychosocial well being. These findings correlated with reverse left ventricular remodelling (r = 0.47) and New York Heart Association (NYHA) symptomatic improvement (r = -0.36). The authors propose that CRT is responsible for these findings either via a haemodynamic mechanism or placebo effect. The usual limitations apply for such work within this area (small sample size, single centre, non randomised study). Furthermore, there was no adjustment of concomitant heart failure therapies following CRT.

From the data presented, it is difficult to draw definitive conclusions. It may well be the case that erectile dysfunction is a surrogate marker of generalised mental well being. This hypothesis is supported by the association between an improvement in NYHA functional class and libido and erectile dysfunction.

CRT has been shown to improve numerous cardiac parameters and surrogates including (but not exclusively) exercise tolerance, symptoms, left ventricular remodelling and mortality. The extra cardiac benefits are less well documented. The study is an interesting observation which, as stated by the authors, requires further work within this area. In particular, there should be a focus on elderly and ischaemic patients. It remains of interest to see whether such initial findings would be replicated in more representative cohorts undergoing CRT implantation.

Authors

Dr Kaushik Guha

Dept of Cardiology, Royal Brompton Hospital, Royal Brompton & Harefield NHS Foundation Trust, Sydney Street, London, SW3 6NP

Dr Rakesh Sharma

Consultant Cardiologist

National Heart & Lung Institute, Imperial College London, Dovehouse Street, SW3 6LY

Corresponding Author:

Dr Kaushik Guha

Clinical Research Fellow in Cardiology

Division of Heart Failure, Department of Cardiology

Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK

Email: k.guha@rbht.nhs.uk

Tel: +44 207 351 7716

Fax: +44 207 351 8148

References

1 Vural A, Agacdiken A, Celikyurt U, et al.  Effect of Cardiac Resynchronization Therapy on Libido and Erectile Dysfunction. Clin Cardiol 2011; DOI:10.1002/clc.20918.

The report recommends new levels of transparency, with the relevant content of dossiers prepared by companies when submitting their devices disclosed to physicians, to illustrate their technical performance before use.  The ESC report also calls for comprehensive registries of devices and their outcomes, with every physician having a responsibility to report complications of device.

Professor Alan Fraser, who chaired the ESC Policy conference on device evaluation, commented to Arrhythmia Watch: “We should ask what clinical evidence has been collected to support their use, before advising managers which devices to purchase for our patients”.  He urges cardiologists to “contribute to registries which monitor the performance of implanted devices, and…report any instances of unexpected device failure promptly”.  Both a lack of transparency regarding specific data, and of registries compiling high-risk devices were key problems listed by a survey² which accompanied the Dispatches investigation, published recently in BMJ Open.

Chief Executive of the Medicines and Healthcare products Regulatory Agency (MHRA) Kent Woods expressed concerns about the current system when interviewed by investigators, but said that “if we were to inhibit innovation by imposing a more burdensome regulatory regime we would have to have some extra evidence that the burden actually provided a greater degree of patient safety”.  The ESC report asserts that such thinking “ignores the fact that some innovations are led by advances in technology (‘solutions seeking applications’) rather than being produced in response to identified clinical needs,” further insisting that “being at the forefront of technological advances also implies responsibilities to ensure that new treatments are safe and effective”.

The ESC report also recommends that obtaining expert advice should be an integral part of the regulatory process, representatives being nominated by major medical associations in Europe to be members of the main advisory committees.  “Academic experts should produce detailed recommendations on how the clinical performance of high-risk (class III) medical devices should be established,” Fraser said.

Legislative decisions on the matter are to be taken by the European Council and the European Parliament in the next few years.  Professor Fraser asserts that major change will not come easily, and any cardiologist wishing to see improvements must seize their chance to influence the debate: “The ESC, with colleagues from other medical associations, is now considering recommendations for cardiovascular implantable electronic devices. The preliminary proposals will be presented at a special session during the ESC Congress in Paris on 28th August 2011”.

References

1 Fraser AG, Daubert  JC, Van de Werf F, et al. Clinical evaluation of cardiovascular devices – principles, problems, and proposals for European regulatory reform. Report of a policy conference of the European Society of Cardiology. Eur Heart J. Doi 10.1093/eurheartj/ehr171.

2 Heneghan C, Thompson M, Billingsley M, Cohen D.  Medical-device recalls in the UK and the device-regulation process: retrospective review of safety notices and alerts. BMJ Open 2011. doi:10.1136/bmjopen-2011-000155.

Reproduced courtesy of J Am Coll Cardiol

The study found a strong association between pericardial fat volumes and the presence, symptom burden (evaluated using the University of Toronto Atrial Fibrillation Severity Scale²) and chronicity of AF (all p values <0.05).  Their results also showed links between pericardial fat deposits and left atrial volume (p < 0.001).  These associations persisted after multivariate adjustment and additional adjustment for body weight.

The authors claim that although studies with larger samples have previously reported associations between systemic adiposity and AF, their finding that pericardial fat but not systemic adiposity was significantly associated with AF suggests that pericardial fat depots may be a more influential measure than either body mass index or body surface area. Their results support the hypothesis of a local pathogenic effect of pericardial fat on the arrhythmogenic substrate supporting AF.

References

1 Wong CX, Abed HS, Molaee P, et al. Pericardial Fat Is Associated With Atrial Fibrillation Severity and Ablation Outcome. J Am Coll Cardiol 2011;57:1745–51.

2 Dorian P, Jung W, Newman D, et al. The impairment of health related quality of life in patients with intermittent atrial fibrillation: implications for the assessment of investigational therapy. J Am Coll Cardiol 2000;36:1303–9.

Results show that women were less likely to:

– Receive beta-blocker: 75.76 % of women received beta blockers in comparison to 79.24% of men (p<0.01).

– Receive lipid-modifying agents: 56.37 % of women received lipid-modifying agents compared to 65.44% of men (p<0.0001).

– Receive angiotensin-converting enzyme (ACE) inhibitors – 55.52% of women received ACE inhibitors compared to 59.99% of men (p<0.01).

The authors, led by Dr Raffaele Bugiardini, University of Bologna, attribute the disparity to multiple factors. After adjusting for age, the presence of congestive heart failure, and whether or not the patient underwent catheterisation, women still received fewer ACE-inhibitors and lipid lowering drugs than men.

A second study² led by Dr Nina Johnston of Uppsala University Hospital, examined the use of CV medications and diagnostic coronary angiography in 7,195 men and 5,005 women with suspected coronary artery disease (CAD), after experiencing chest pain,
between 2006 and 2008. Results showed that prior to undergoing angiography 83% of women had been prescribed aspirin in comparison to 86.1 % of men (p=0.001).

The study also showed that in the youngest age group (aged <59 years) 78.8% of women who underwent angiography were found to have normal/ non-significant CAD in comparison to 42.3% of men (p<0.001), and furthermore that 18.2% of men were diagnosed with left main or three vessel disease compared to 4.2% of women (p<0.001). This, say the authors, underlines the difficulty faced by clinicians in diagnosing CAD in women.

The studies accompany recent calls from the European Society of Cardiology (ESC) for action to reduce the gender disparities suggested by such results. “The ESC wants to raise awareness, among both cardiologists and the public, that women still are not receiving equal access to medical treatments and also are not being represented sufficiently in clinical trials,” said Marco Stramba Badiale, an ESC spokesman on women’s issues from IRCCS Istituto Auxologico Italiano, Milan.

“The problem is that despite female gender being associated with worse CV outcomes there are still major misconceptions among both health professionals and the public that CVD is not as serious in women as men…if physicians see women aged 55 to 60 years with atypical symptoms in the emergency room they don’t automatically think of heart attacks”.

Women must be included in RCTs

The ESC are calling upon the European Medicines Agency (EMA) to make the fair representation of women in clinical trials a requirement for the licensing of all pharmaceutical agents. This is supported by Work Package 6 of the EuroHeart project, a study that was undertaken by the ESC in conjunction with the European Heart Network. The study reviewed 62 randomised clinical trials published since 2006, finding that out of 389,891 participants, 33.5% were women, and that additionally only 50% of trials reported their analysis by gender.

“It’s very important that data concerning women is analysed separately because there are often differences in the pharmacodynamics, pharmacokinetics and physiology in comparison to men, making it possible that the efficacy of drugs might be completely different in women,” said Stramba-Badiale.

The American Heart Association (AHA) has taken action against gender inequality in a recent update to its Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women.4 While a previous update in 2007 stipulated a >20% risk of coronary heart disease (CHD) in the next 10 years as criteria for ‘high risk’, the new guidelines lower the threshold to a >10% risk of dying from any CV event in the next 10 years.

The guidelines acknowledge that there is increasing concern amongst patients and clinicians over the management of CHD in women, and that there have been improvements in CVD risk factor awareness, treatment, and control. The authors state that future improvements will require “concerted efforts toward further research and the dissemination and implementation of lifestyle and treatment interventions,” as well as a “focus on incorporating multidimensional, interactive systems to increase accountability among payers, healthcare professionals, and patients for cardiovascular preventive care in women”
References

1. R Bugiardini. AT Yan, RT Yan et al. Factors influencing underutilization of evidence-based therapies in women. European Heart Journal. Doi: 10.1093/eurheartj/ehr027.
2. N Johnston, K Schenck-Gustafsson, B Lagerqvist et al. Are we using cardiovascular medications and coronary angiography appropriately in men and women with chest pain? European Heart Journal. Doi: 10.1093/eurheartj/ehr009
3. Towfighi A, Zheng L, Ovbiagele B. Sex-specific trends in midlife coronary heart disease risk and prevalence. Arch Intern Med. 2009;169:1762-6.
4. Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guidelines for the prevention of CVD in women—2011 update. A guideline from the American Heart Association. Circulation 2011;123:1243-62.