Yearly Archives: 2015

Pulmonary hypertension news from AHA and ERS

Br J Cardiol 2016;23:(1) Leave a comment
Click any image to enlarge
Authors:
Sponsorship Statement: Actelion have funded the production of this article but have had no input into content

First published online December 8, 2015

We report highlights of pulmonary hypertension presentations from the most recently held European Respiratory Society (ERS) congress, held in Amsterdam, the Netherlands, from 26th–30th September 2015, and also from the American Heart Association (AHA) Scientific Sessions, held in Orlando, USA, from 7th–11th November 2015.

News from ERS

High levels of anxiety and depression in PH

Psychological morbidity remains under-diagnosed in pulmonary hypertension (PH), and one third of patients suffer from depression and/or anxiety for which only 38% are being treated, according to a study conducted by Dr Gina Somaini and colleagues (University Hospital of Zurich, Switzerland). They investigated the prevalence and course of anxiety and depression and their association with health-related quality of life (HRQoL) disease markers and survival over a mean period of 16 months.

In the study, 45 newly diagnosed and 86 pretreated patients with arterial and chronic thromboembolic PH had repeated assessments of the Hospital Anxiety and Depression Scale (HADS), HRQoL, six-minute walking distance (6MWD) and New York Heart Association functional class.

According to HADS, 33% of PH patients suffered from depression and 34% had anxiety. Of these patients, 38% were in treatment for their depression or anxiety. Scores improved within six months after the introduction of PH-targeted treatment and survival was worse in patients with anxiety (p=0.014) (abstract PA2112*).

New QoL score tested

Dr Beatriz Garcia-Aranda and workers (Royal Brompton Hospital, London) described a new, easy-to-use quality of life (QoL) questionnaire, emPHasis-10, based on 10 key questions designed for use in PH patients. They reported experience in using this score and its relation to markers of disease severity in 174 patients. The emPHasis-10 score was found to be significantly associated with established predictors of exercise intolerance and prognosis. However, further studies are needed to provide cut-offs, which can be used to introduce or escalate disease-specific therapies in PH (abstract PA3776*).

Benefits with initial combination therapy?

There is little data on the use of initial dual oral combination therapy for pulmonary arterial hypertension (PAH) in current practice. Dr Caroline Sattler (Hôpital Bicêtre, Université Paris-Sud, France) obtained clinical and haemodynamic data from 52 newly diagnosed PAH patients from the prospective French PAH registry, who were on initial combination treatment (endothelin receptor antagonist and PDE-5 inhibitor) at baseline and at first evaluation (3−6 months). Initial dual oral combination therapy in patients with PAH reduced pulmonary vascular resistance (PVR) by 40% at 3−6 months, and was associated with an 82% survival rate at three years. Dr Sattler and her co-workers conclude that an initial combination therapy strategy is appealing but it needs to be properly compared to sequential combination therapy (abstract PA3775*).

Feasibility of exercise training in PAH

In PAH, strong evidence supports prescribed exercise to safely improve QoL, haemodynamics and exercise capacity. Currently no dedicated PAH rehabilitation programme exists in the UK. Drs Alison Mackenzie and Martin Johnson (Golden Jubilee National Hospital, Glasgow) sought to determine the acceptability of rehabilitation with the aim of developing a PAH specific exercise programme. Patients attending the Scottish Pulmonary Vascular Unit were invited to participate in a survey. A PAH rehabilitation programme was described. Patients were asked if they would be interested in all components, specific components or none. Responses were received from 43% (97/224), of whom 62.8% (61/97) were interested in all components, and 73.2% (71/97) in outpatient rehabilitation. Those interested were younger and trended towards worse QoL scores and were more likely to have idiopathic PAH.

Results showed that exercise training in PAH is acceptable. Based on free comments from patients, barriers may be employment, a dependant family member, or other limiting comorbidities. The authors conclude that they have demonstrated sufficient enthusiasm to pursue this as a promising treatment option in the UK (abstract PA3779*).

Adherence to medication should be better

Little is known about the level of adherence to PH specialist medicines and the factors that may determine it. Duncan Grady and colleagues (Pharmacy Department, Papworth Hospital, Cambridge) investigated this in a study of 262 PH patients (56.9% on monotherapy), who were treated with targeted therapy (sildenafil, tadalafil, bosentan, ambrisentan, iloprost, epoprostenol, treprostinil). The patients completed a Morisky Medication Adherence Scale-8 (MMAS-8) questionnaire (see http://dmorisky.bol.ucla.edu/MMAS_scale.html), either in hospital or at home via postal mail.

Participants were also invited to fill in self-reported pill count questions three months apart. The answers were used to calculate each participant’s medicine consumption across this period. Data from MMAS-8 showed that:

  • 7% reported high adherence
  • 5% moderate adherence
  • 8% low adherence.

The authors conclude that overall adherence seems to be slightly higher than published adherence rates to medicines for other disease groups but over half of the PH patients report suboptimal adherence behaviour. Further work to develop interventions to improve adherence appears to be warranted (abstract PA3786*).

*Abstracts for all ERS sessions can be accessed at: http://myeposter.ersnet.org/my-abstract-book-2015/

News from AHA

AHA produces paediatric PH guidelines

For the first time, guidelines have been developed for children with PH. These were widely discussed at the AHA meeting in Orlando, USA. The joint American Heart Association/American Thoracic Society guidelines are published in Circulation (doi: 10.1161/CIR.0000000000000329).

“These children suffer with health issues throughout their lives or die prematurely – particularly if they’re not properly diagnosed and managed. But with the proper diagnosis and treatment at a specialised centre for pulmonary hypertension, the prognosis for many of these children is excellent,” said Dr Stephen L Archer (Queens University, Kingston, Ontario, Canada) and co-chair of the guideline’s writing committee.

The new guidelines provide practical advice on:

  • classification of PH
  • proven and emerging medical and surgical therapies
  • treatments which are approved for children with PH and the dosages that should be used.

The guidelines also point to gaps in knowledge about paediatric PH and offer advice about issues that parents and healthcare providers struggle with, including whether children should have anticoagulants, how to determine whether a child with PH can safely engage in exercise or travel on a plane, and how high altitude can cause or worsen PH.

The guidelines are available at http://circ.ahajournals.org/content/early/2015/10/29/CIR.0000000000000329.full.pdf+html

Calcification − a new threat in PAH

Canadian workers have, for the first time, demonstrated the presence of significant distal pulmonary artery (PA) calcification, which contributes to disease worsening in PH patients.

Dr Sophie Chabot (CRIUCPQ-University Laval, Quebec, Canada) and her team, using computed tomography (CT) scans, in a study of 50 PAH patients, showed that they had a significant increase in distal PA calcification compared to control patients matched for age, sex and comorbidities known to promote vascular calcification. This non-invasive finding was histologically confirmed in the same patients post lung transplantation. The fact that PAH patients are now living longer increases their odds of developing PA calcification lesions.

This process appears to be related to the upregulation of Runt-related transcription factor 2 (RUNX2), a key osteogenic factor which triggers the development of proliferative and calcified vascular lesions within the lungs, thus worsening PAH. Thus RUNX2 looks to be an attractive new therapeutic strategy to improve PAH according to the authors (Circulation 2015;132:A14631).

Women under-represented in clinical trials

To assess the safety and efficacy of cardiovascular disease (CVD) drugs, including those prescribed for PH, in the diverse population of patients who will use them post-approval, the US Food and Drug Administration (FDA) has implemented guidance and regulation to encourage the inclusion of women and racial/ethnic minorities in drug clinical trials.

A study presented by Dr Emmanuel O Fadiran and colleagues from the FDA Centre for Drug Evaluation and Research (CDER) assessed the participation of women and minorities in clinical trials for CVD indications for New Drug Applications (NDAs) approved at FDA CDER from 2013−2014.

Four novel CVD drugs were approved in this time frame, including two drugs indicated for pulmonary hypertension (PH) (riociguat, total CT population n=2691; macitentan, n=1,884), and one drug each for prevention of thrombotic acute CV events (vorapaxar, n=41,972) and treatment of neurogenic orthostatic hypotension (NOH) (droxidopa, n=1,125).

Results showed that the majority of the trial participants were White (85%), with a mean age of PH patients of 48 years. The proportion of female participation varied substantially by disease indication, with PH (a female-predominant disease) having the highest female participation.

The proportion of female participation was 26% for thrombotic CV events, 40% for NOH, and 47% for PH. Female participation in pivotal trials only (in which benefit-risk was demonstrated) was 24% for thrombotic CV events, 33% for NOH, and 75% for PH.

Female participation in the prevention of thrombotic CV events was lower than anticipated based upon disease prevalence in the population. Further exploration of demographic subgroup participation in clinical trials for CVD drugs in a larger sample size is ongoing (Circulation 2015;132:A11144).

The full abstracts can be accessed in Circulation 2015;132:suppl 3 (November 10th 2015 issue).

Heart Rhythm Congress 2015

Br J Cardiol 2015;22:146 Leave a comment
Click any image to enlarge
Authors:

The 10th Heart Rhythm Congress was held October 4th–7th 2015 at the International Conference Centre (ICC) in Birmingham. This year’s event hosted a wide range of topics including electrophysiology, device management, syncope, inheritable arrhythmias and the basic sciences. Dr Kim Rajappan (Oxford University Hospitals) took on the role of Programme Director for the first time this year. The meeting was a resounding success according to Drs Afzal Sohaib and Kevin Leong, who report on its highlights. This report is carried in full online.

Plenary session – precision medicine for the next decade

Screen shot 2015-11-17 at 12.47.01A distinguished line-up of speakers enlightened the congress on the future of rhythm management in this session. Dr Calum MacCrae (Brigham and Women’s Hospital, Boston, USA) opened our eyes to the ongoing challenges and potential of genetic testing to tailor the treatment of cardiovascular disease.

From genetics and genomics we moved on to proteomics, where Professor Manual Mayr (King’s College London) enlightened us on how this emerging and rapidly growing discipline can shape the future of rhythm management. Professor A John Camm (President, Arrhythmia Alliance) brought the concept of precision medicine back to a very real and everyday clinical scenario we face with the use of non-vitamin K oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation (AF), and the myriad different features which the different agents offer us to optimise and tailor our choice of agent to individual patients, with their individual preference and individual clinical scenario.

Finally Professor Sanjiv Narayan (Stanford University, USA) very charismatically spoke about how findings from current clinical research in arrhythmia therapy can guide tailored approaches to ablation therapy, including his pioneering work on ablating electrical rotors and focal impulses in AF.

Management of syncope and POTS

An overview of the recently published 2015 Heart Rhythm Society consensus statement on the management of postural orthostatic tachycardia (POTS), vasovagal syncope and inappropriate sinus tachycardia was given by Professor Richard Sutton (Monte Carlo, Monaco) and Dr Satish Raj (University Of Calgary, Canada). All three conditions and a summary of guidance and recommendation as to their management was given. It differs from current European Society of Cardiology (ESC) guidelines in the definition of syncope, but incorporates some new advice on pacing and tilt-testing from European work. Professor Sutton also added the ESC has started to revise its Guidelines in Syncope due in 2017. Changes will include an online compendium of ‘how to perform’ and ‘how to interpret’ relevant tests.

The European Heart Rhythm Association consensus document on syncope units was presented by Professor Rose Anne Kenny (Trinity College Dublin, Ireland). She presented data showing the wide variation in practice of syncope evaluation and in adoption of recommendations from published guidelines from personal and other published works highlighting the rationale and requirement for the development of services.

She added that a syncope service should have a multi-disciplinary approach drawing from the specialties of cardiology, neurology, geriatrics and psychiatry. A robust discussion ensued on the barriers to setting up such a service with anecdotal solutions and suggestions coming from the speaker, chair and members of the floor.

Treatment of ventricular arrhythmias

This session opened with an erudite overview of the development of ventricular arrhythmia management over the last 30 years by Professor Camm. Subsequent speakers expanded on each of these developments starting with pharmacotherapy by Dr Lluis Mont (Hospital Clinic of Barcelona).

Professor Richard Schilling (London Bridge Hospital) provided an insightful talk on the evolving role of catheter ablation, touching on some newer technologies such as force sensing and newer mapping techniques to improve outcomes. Other topics included the strategies in managing ventricular ectopy and use of cardiac magnetic resonance imaging (MRI) in determining the substrate to guide and improve ablation.

Highlights from the scientific sessions and posters

The scientific sessions saw contributions of cutting edge research from several tertiary institutes across the UK that focussed on elucidating the mechanisms of arrhythmias. Although rotors have been shown to drive AF and targeting these sites has become an emergent ablation strategy, factors that influence rotor location and stability remain unclear.

Dr Fu Siong Ng (Imperial College London) addressed this, employing optical mapping experiments on canine atrial tissue to show anatomical locations such as the pulmonary veins, and functional factors such as spatial heterogeneities in conduction and repolarisation, were more important determinants of rotor sites than regions of fibrosis. These mechanistic insights could optimise ablation therapy by identification of such factors in vivo with emerging imaging modalities.

Action potential duration alternans (APDA), or the periodical change of action potential duration in the heart, is a precursor of ventricular fibrillation and associated with sudden death, although the underlying mechanisms for this still remain undetermined. Professor Pier Lambiase’s group (University College London/Bart’s Heart Centre) addressed this by firstly demonstrating that different sites of the heart possess different degrees of susceptibility to APDA and described how action potential duration in these areas of the heart respond to rising heart rates.

He then demonstrated using mRNA studies from biopsied tissue, that such areas of myocardial tissue susceptible to APDA have greater expression of specific ion channel repolarisation currents and calcium handling molecules, providing molecular insights into this pro-arrhythmogenic phenomenon.

In other presented work, other institutes showcased the potential use of novel electrocardiogram- (ECG) based biomarkers (University of Leicester) and non-invasive electrocardiographic imaging technology (National Heart and Lung InstituteNHLI) to risk stratify risk and gain arrhythmogenic insights into repolarisation disorders (e.g. Brugada Syndrome). The conference also hosted a series of useful primer sessions for those wishing to gain a greater understanding of research in the basic sciences. Thoughtful and jargon-free lectures were delivered on the basics of genetics, the applications of computer modelling and simulation, along with enlightening lectures on the use of various stem cell technologies and animal models (e.g. zebra fish) as research and clinical tools.

10th anniversary awards and reception

The ICC hosted the 10th Anniversary Awards.  Professors John  Camm (, President of Arrhythmia Alliance), and Professor Nick Linker (, President of the British Heart Rhythm Society) (BRHRS) presided over the ceremony, where .  Trudie Lobban MBE spoke of her pride in at seeing this meeting grow in the last decade from a potential group of around 150 participants to the huge meeting we see today.

Prizes were awarded to Dr Joseph de Giovanni of, Birmingham Children’s Hospital (Individual who has Contributed to Arrhythmia Services), the Westcliffe Community Cardiology Service (Team of the Year), and to Lloyds Bank Berkshire Lloyd Berkshire (Charles Lobban Volunteer of the Year).  Professor Blair Grubb, (University of Toledo Medical Center, Ohio, USA), received the award of for Medical Professional of the Decade for his work on syncope and dysautonomiadysautonomia.

Young Investigators’ Competition

Six cardiology registrars showcased their research to the Congress and received a grilling from Professor’s Andre Ng, Andrew Rankin, Pier Lambiase, and Dr Francisco Leyva-Leon.  The competition was divided into two categories: electrophysiology and device therapy.  The electrophysiology category was won by Dr Norman Qureshi (Imperial College London) for his abstract entitled ‘”Characterisation of the persistent AF substrate through the assessment of electrophysiologic parameters in the organised versus disorganised rhythm,’” where he explained how during his research he tried to dissect the structural and functional components underlying the mechanisms of atrial fibrillation.

Runners up in this category were Dr Gavin Chu (University of Leicester) for his work on targeting the cyclical highest dominant frequency in the ablation of persistent AF, and Dr Henry Chubb (King’s College London) for his work looking at real time MRI- guided ablation of arrhythmias, moving on pre-clinical work by the group to clinical application.

The device category was won by Dr James Gamble (University of Oxford) for his abstract entitled ‘”Differential relationship of electrical delay with endocardial and epicardial left ventricular leads for cardiac resynchronisation therapy.’”  Dr Gamble used data from the Oxford groups work on trans-ventricular septal approach to biventricular pacing to demonstrate improved electrical characteristics when the left ventricle is paced via the endocardium rather than epicardium.

 Runners up in this category were Dr Afzal Sohaib (Imperial College London) who presented data on the role of improved atrioventricular (AV) timing and its contribution to the benefits in biventricular pacing, and how AV optimised direct His bundle pacing may open a new frontier in the treatment of heart failure, and finally Dr Robin Taylor (University of Birmingham) presented data  on the use of feature tracking and contrast enhanced MR to understand the importance of lead position in relation to the presence of scar for identifying the areas of latest mechanical activation.

Concerns for the future

An ongoing concern throughout the meeting both during the sessions and in break- out areas were concerns related to new tariffs for electrophysiology and device therapy in the National Health Service (NHS), and the potential for this to destabilise heart rhythm services in the UK.  The meeting formed an effective forum for different stakeholders to come together to try find solutions to prevent patients from losing out on life saving and life changing therapy offered by heart rhythm specialists.  Let us hope this will not be a feature for 2016 and we can focus on all the other excellent work instead!

Dr Afzal Sohaib
British Junior Cardiologists’ Association President and Electrophysiology Fellow
Imperial College Healthcare NHS Trust

Dr Kevin Leong
Clinical Research Fellow in Cardiac Electrophysiology
Imperial College London

‘Lipids in the community’ – HEART UK 29th annual conference

Br J Cardiol 2015;22:145 Leave a comment
Click any image to enlarge
Authors:

‘Lipids in the community’ was the general theme of this year’s HEART UK conference, attended by 200–250 participants, covering primary and secondary care, patients and industry. The event was held at the University of Hertfordshire from 16th–18th September 2015. General Practice Nurse Jaqui Walker reports some of its highlights.

Screen shot 2015-11-25 at 12.33.35

Detecting undiagnosed familial hypercholesterolaemia (FH) in the community and helping families manage the condition before it leads to a cardiovascular disease (CVD) event was one of the key themes of the conference.

A second important theme was taking action on the risk factors and behaviours that are linked to CVD and other non-communicable diseases (NCDs). These risk factors and behaviours have been understood for decades, yet the challenges of finding effective ways to help the population change to healthier behaviours, and how to assess and monitor this in clinical practice, remain.

Professor Huon Gray, National Clinical Director for Heart Disease, NHS England
Professor Huon Gray, National Clinical
Director for Heart Disease, NHS England

In his opening address Professor Huon Gray (National Clinical Director for Heart Disease, NHS England) discussed the Department of Health (DOH) 2013 Cardiovascular Outcomes Strategy,1 which has been instrumental in raising the profile of FH. As a result of this strategy an FH steering group with multi-representation was established. Its achievements have included:

  • Funding by the British Heart Foundation (BHF) of FH nurses to cover 20 million people in England. These are pump-primed positions and will need to be funded locally by commissioners once BHF funding finishes.
  • Meetings with the Chief Executive of Public Health and the Medical Director at NHS England, and at the Kings Fund and British Cardiovascular Society, have helped to raise the profile of FH, and to put FH detection and management on the agenda.
  • 100,000 genome project with the inclusion of FH candidate genes.
  • A greater understanding of the prevalence of FH.
  • An agreement by the National Institute for Health and Care Excellence (NICE) to revise their FH clinical guidelines in 2016, due to the reduction in statin costs, and the likelihood that FH is more common than previously thought.

Currently the pathway for the detection and management of hyperlipidaemia is complex and disjointed but Professor Gray spoke with optimism for the future; he believes that hyperlipidaemia and, in particular, FH is gaining traction and beginning to be seen as a priority area for action. Personalised medicine and genetics will help, as FH is easily detectable and treatable. Progress is being made; disease prevention is high on the political agenda, especially with the governments ‘Five Year Forward View,’2 and there will be more progress in the future.

How do we manage high-risk patients?

Dr Dev Datta (University Hospital Llandough) tackled the subject of dealing with high-risk patients. Dr Datta defined a high-risk patient as: “A patient [for whom] through a multiplicity of risk factors, or the severity of one or more of them, a first or recurrent cardiovascular event is considered likely within a defined timescale.”

He explained that as healthcare professionals (HCP) we are often tempted to look at snapshots when what is actually important is the cumulative burden from risk factors over decades. It is for this reason that Dr Datta is in favour of lifetime risk calculators.

He presented some case studies and with these made a number of points. Firstly, he emphasised the importance of seeing the whole patient and considering a differential diagnosis e.g. hypothyroidism, liver disease, renal disease etc… Secondly, he looked at multifactorial risks. Patients with multiple risk factors can be a challenge to manage and this is often easier within a multidisciplinary team. The intervention may be more “discussion and behaviour change driven,” which is potentially more difficult and time consuming than medical treatments such as drugs.

The role of apheresis, which in simplistic terms could be described as dialysis for cholesterol, was examined. In the case of high-risk motivated patients (e.g. FH patients) this treatment can be highly effective. It is well tolerated but is costly and often involves a long journey to reach a centre where the treatment is available.

Emerging novel drug therapies, e.g. PCSK9 inhibitors, will offer a new avenue for patients who are at high risk due to their lipid profile.

Heart health a global issue with global strategies

A global perspective for cardiovascular disease was delivered by Professor David Wood (St Mary’s Hospital, Imperial College, London). In 2011 the Heads of State met to debate and agree a global strategy for NCDs. As a result, nine voluntary global NCD lifestyle, medicines and risk factor targets were developed and the ‘25 by 25’ agenda (to reduce premature disease from NCD by 25% globally by 2025) was agreed. The INTERHEART study3 conducted worldwide to look at the causes of CVD has shown that the relationship between risk factors and myocardial infarction (MI) is the same in every region of the world.

The World Heart Federation has adopted the ‘25 by 25’ strategy with a focus on CVD prevention. They highlight the need for partnerships and coalition building across all health disciplines in order to speak with one voice for CVD prevention and the importance of developing reliable health information systems in order to be able to monitor and measure what is being achieved in terms of cardiovascular mortality, morbidity and health behaviour. In the UK JBS3 (representing 11 professional organisations) signed up to a common agenda as an example of this sort of coalition.

The World Heart Federation has developed road maps for CVD prevention. They focus on secondary prevention of CVD, hypertension control and tobacco control in order to help achieve the ‘25 by 25’ aspiration. This is because 80% of CVD events occur in people with previous CVD, hypertension or who smoke. The roadmaps look at health policy, systems, availability and affordability of treatments, accessibility of preventative care, acceptance and adherence by patients to treatment over a lifetime. In essence they assess the entire picture of how to get from the current CVD healthcare environment to the aspiration of a 25% reduction in mortality by 2025. Methods of bypassing roadblocks to patients getting care are also included, making the roadmaps a very useful tool.

Variation occurs between countries depending on culture, health systems and health economy. The World Health Organization (WHO) targets for the use of priority interventions are not being achieved in most parts of the world. In addition many patients do not get the benefit from recommended programmes such as a comprehensive cardiac rehabilitation. The implementation of evidence into effectiveness is a great challenge throughout the world.

Familial hypercholesterolaemia – what will the future hold?

Professor Steve Humphries, London (Myant lecturer 2015)
Professor Steve Humphries, London (Myant
lecturer 2015)

The Myant Lecture on the molecular genetics of FH was presented by Professor Steve Humphries (University College London [UCL]). Professor Humphries retires this year but will be continuing as Emeritus Professor at UCL, dedicating his time to FH. It will be interesting to look back 10 years after this lecture and see how far FH has developed. This session commenced with recognition of Nicolas Bruce Myant (1917–2015) and his lifelong passion for science and dedication to the field of lipidology.

Professor Humphries explored the history of FH gene discovery and the possibility of a fourth gene being discovered in the future. The current three genes and their frequency and severity were discussed. All three FH-causing genes have led to novel treatments. The discovery of low-density lipoprotein receptors (LDLR) led to the development of statins, apolipoprotein B (apoB) to antisense agents such as mipomersen, and PCSK9 to monoclonal antibodies.

It is now possible and relatively affordable to carry out deep sequencing of the whole genome or exome. The current issue is with bioinformatics. The laboratories are figuratively drowning in data – it is a problem even to store all the data, let alone analyse it!

Two new genes were identified as potentially interesting candidates; CH25H (Cholesterol 25-Hydroxylase) and INSIG2 (Insulin-induced gene 2).

Patients with DNA positive results for FH need early drug therapy and efficient relative testing (cascade testing). The frequency of FH was previously thought to be around 1/500 people, although recent data suggests 1/250 people maybe a more accurate prediction. This 1/250 frequency of FH would mean there are 240,000 monogenic FH patients to find in the UK. In 2016 the 100,000 genome project may find 200–400 new FH patients and cascade test their relatives.

The impact of undiagnosed FH presents a high burden to society with 50% of males experiencing MI before the age of 50, and 60% of females before the age of 60. Less than 10% of those predicted to have FH in the UK have been identified.

Obesity – focusing on what really matters

Professor Jean-Pierre Després, Quebec, Canada
Professor Jean-Pierre Després, Quebec,
Canada

Professor Jean-Pierre Després (Quebec Heart and Lung Institute, Canada) examined the issue of obesity. He described obesity as a lifestyle marker not a disease, and stated that the medical model is not well designed to tackle it. He explained that the actual risk from obesity is largely determined by too much fat being stored in the wrong place; it is abdominal fat that is the problem.

Professor Després argued that improving cardiovascular fitness and reducing the waistline are better targets for CVD health than weight loss. With the current epidemic of chronic NCDs which are responsible for 60% of deaths worldwide, the WHO have identified four common risk behaviours: tobacco use, high alcohol consumption, poor nutritional quality of the diet and a lack of physical activity.

Simple tests to assess cardiovascular fitness and waist circumference are required. A tremendous opportunity is being missed if health behaviours are not measured and targeted effectively in clinical practice. Four variables should be assessed (Després 2015):

  • Abdominal obesity
  • Nutritional quality
  • Cardiorespiratory fitness
  • Physical activity habits.

Professor Després concluded that in our environment, non-healthy behaviours are often the easy behaviours – instead we need to reshape the environment so that healthy behaviours become the easy ones. This will require an individual- as well as a population-based approach.

Carbohydrates and heart health

Professor Bruce Griffin (University of Surrey) delivered an interesting talk exploring the role of dietary carbohydrate in heart health. He explained that carbohydrates are a diverse group of macronutrients, and the focus of his presentation was on the carbohydrates with the strongest and most consistent evidence for an association with disease. In a positive, protective sense this is dietary fibre and in an adverse way, although with more controversial data, free sugars. The Scientific Advisory Committee on Nutrition (SACN ) have issued new guidelines5 with recommendations to eat more dietary fibre (30 g/day) and cut sugar to less than 5% of total energy.

There is consistent evidence for the cholesterol-lowering effect of β-glucan shown in a meta-analysis of randomised controlled trials.6 A change in low-density lipoprotein cholesterol (LDL-C) of approximately 0.3 mmol/l occurs. Professor Griffin compared this to the use of plant sterols/stanols and described β-glucan from oats/barley etc… as about half as effective as stanols and sterols, but still a useful part of a portfolio of dietary measures to cut cholesterol.

Professor Griffin explored the role of dietary free sugar and concluded that, at high levels of intake almost twice the national average (>20% total energy), sugar has been shown to produce adverse metabolic effects that include increasing levels of internal fat, most notably in the liver. At lower levels of intake, the energy from sugar can contribute to weight gain and obesity. While the latter effect of sugar on body weight will increase cardiovascular risk in populations, subgroups of individuals with pre-existing non-alcoholic fatty liver disease may show increased sensitivity to the adverse effects of free sugars that are independent of body weight.

References

1. Cardiovascular disease outcomes strategy: improving outcomes for people with or at risk of cardiovascular disease. Department of Health, 2013. Available from: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/217118/9387-2900853-CVD-Outcomes_web1.pdf

2. Five year forward view. National Health Service, 2014. Available from: https://www.england.nhs.uk/wp-content/uploads/2014/10/5yfv-web.pdf

3. Rosengren A, Hawken S, Ounpuu S, et al. Association of psychosocial risk factors with risk of acute myocardial infarction in 11,119 cases and 13,648 controls from 52 countries (the INTERHEART study): case-control study. Lancet 2004;364:953–62.

4. Després JP. Obesity and cardiovascular disease: weight loss is not the only target. Can J Cardiol 2015;31:216–22. http://dx.doi.org/10.1016/j.cjca.2014.12.009 

5. SACN Carbohydrates and health report. Public Health England 2015. Available from: https://www.gov.uk/government/publications/sacn-carbohydrates-and-health-report 

6. Whitehead A, Beck EJ, Tosh S, Wolever TMS. Cholesterol-lowering effects of oat b glucan: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2014;100:1413–21. http://dx.doi.org/10.3945/ajcn.114.086108

In brief

Br J Cardiol 2015;22:143–4 Leave a comment
Click any image to enlarge
Authors:

News in brief from the world of cardiology

BHF to spend half a billion pounds on research

A new research strategy has been launched by the British Heart Foundation (BHF), aiming to fund over half a billion pounds of new cardiovascular research over the next five years.

The BHF’s new strategy includes a commitment to continue funding the best researchers working across all areas of cardiovascular disease research.  This includes a pledge by the BHF to help women stay in research after a review highlighted the underrepresentation of women in senior cardiovascular research roles. Also, for the first time, the BHF will fund healthcare professionals, such as nurses, by establishing a dedicated grant scheme. This research is aimed at improving the quality of care for people with cardiovascular disease.

Valsartan/sacubitril receives EC authorisation

The European Commission (EC) has granted marketing authorisation to valsartan/sacubitril (Entresto™, Novartis) for the treatment of adult patients with symptomatic chronic heart failure and reduced ejection fraction (HFrEF).

The decision, which follows previous approvals in the USA and Switzerland, is based on results from the 8,442-patient PARADIGM-HF study in patients with HFrEF, which was stopped early when it was shown valsartan/sacubitril significantly reduced the risk of cardiovascular death versus enalapril.

At the end of the study patients who were given valsartan/sacubitril were more likely to be alive and less likely to have been hospitalised for heart failure than those given enalapril. Analysis of safety data showed that the combination drug had a similar tolerability profile to enalapril.

Novartis is hoping valsartan/sacubitril will be available in the UK before the end of 2015. Patients who are currently receiving the drug under the Early Access to Medicines Scheme will be able to continue to do so until the Health Technology Assessment completes its appraisal of the medicine, anticipated in 2016.

Alirocumab available for hypercholesterolaemia

Alirocumab (Praluent®, Sanofi) is now available for certain adult patients with hypercholesterolaemia in the UK, following its authorisation by the European Commission (EC).

The drug is authorised for use in patients who are unable to reach their low-density lipoprotein (LDL) cholesterol treatment goals, despite modifying their diet and taking a maximum tolerated dose of a statin and/or other lipid-lowering therapies. These patients include those with: high levels of LDL cholesterol; heterozygous familial hypercholesterolaemia (HeFH); and patients who are statin intolerant, or contraindicated.

The UK Chief Investigator of three clinical studies involving alirocumab, Dr Adie Viljoen (Lister Hospital, Hertfordshire), said: “Alirocumab will provide high-risk patients with HeFH and those with high cardiovascular risk who have not responded adequately to optimal lipid-lowering intervention including lifestyle modification and treatment with high intensity statins, a new option to reduce their cholesterol levels with the aim of reducing their risk of heart attack and stroke”.

New NICE quality standard targets MI and stroke risk

The latest quality standard published by the National Institute for Health and Care Excellence (NICE) aims to prevent thousands of people from becoming ill and dying prematurely from myocardial infarction (MI), strokes and peripheral arterial disease. The quality standard covers identifying and assessing cardiovascular risk in adults, and, where it’s necessary, using statins to reduce levels of harmful cholesterol in order to prevent cardiovascular disease (CVD).

The quality standard includes nine statements aimed at healthcare professionals caring for people in danger of developing CVD, or who already have CVD. These include:

  • Adults under 85 who have been identified with an estimated increased risk of CVD are offered a full formal risk assessment using the QRISK2 tool
  • Adults with a 10-year risk of CVD exceeding 10%: receive advice on lifestyle changes before any offer of drug intervention; and are assessed for secondary causes of hyperlipidaemia before any offer of statin therapy
  • Adults with a 10-year risk of CVD exceeding 10% for whom lifestyle changes are ineffective or inappropriate have a discussion on the risks and benefits of starting statin therapy.

Professor Gillian Leng (Deputy Chief Executive and Director of Health and Social Care at NICE) said: “Like the NICE clinical guideline on which this quality standard is based, we’re not saying that everyone who is assessed as having a 10% or greater risk of developing CVD within 10 years should be given a statin. Before that happens there are many things that people can do to reduce their risk, and the standard is clear that making changes to lifestyle is the first consideration”.

New UK guidelines on resuscitation

A new set of guidelines has been released by the Resuscitation Council (UK). This year’s guidance contains no significant changes to core interventions or processes, instead emphasising the importance of implementation and quality assurance to try and improve patient outcomes.

Out of hospital, there should be increased public involvement in the recognition of cardiac arrest, in calling the emergency services, in starting cardiopulmonary resuscitation (CPR), and in locating and using an automated external defibrillator (AED) as quickly as possible, say the guidelines. Healthcare professionals are encouraged to help with this by offering and supporting training initiatives wherever appropriate, particularly to schoolchildren.

The new guidelines also: identify key areas for improvement regarding survival after an in-hospital cardiac arrest, examine new evidence showing the value of waveform capnography in clinical assessment, and outline the importance of decisions surrounding end-of-life care and whether or not to attempt CPR.

New tropinin I test may rule out MI faster

A recent large study conducted by researchers at the University of Edinburgh shows a new high-sensitive troponin-I (hsTnI) test may help rule out myocardial infarction (MI) faster to help earlier discharge in two thirds of patients presenting with chest pain at A&E (Accident and Emergency).

Currently troponin blood testing is done at A&E admission, and then again within 12 hours, to evaluate whether or not patients are having MIs.

The prospective observational cohort study of over 6,000 patients published in the Lancet (doi: 10.1016/SO140-6736(15)00449-3), using Abbott’s Architect stat high sensitive troponin-I (hsTnl) suggests that by using a newly identified and precise single troponin testing level (<5 ng/L), doctors have the potential to double the number of patients who are discharged directly from A&E, which could reduce waiting times, and avoid repeat testing and hospital admission.

In an editorial comment on the British Heart Foundation funded study, Dr Louise Cullen from the Department of Emergency Medicine, Royal Brisbane and Women’s Hospital, New Zealand and colleagues, describe the study as “a huge advance in the assessment of patients with possible acute coronary syndrome in emergency departments”.

Clopidogrel does not reduce mortality or increase cancer

A report from the US Food and Drug Administration (FDA) has determined that long-term use of the antiplatelet drug clopidogrel does not increase or decrease overall risk of death in patients with, or at risk for, heart disease. FDA evaluation of the DAPT (Dual Antiplatelet Therapy) trial and several other clinical trials also does not suggest that clopidogrel increases the risk of cancer or death from cancer.

The FDA performed meta-analyses of other long-term clinical trials to assess the effects of clopidogrel on death rates from all causes. The results indicate that long-term (12 months or longer) dual antiplatelet therapy with clopidogrel and aspirin do not appear to change the overall risk of death when compared to short-term (six months or less) clopidogrel and aspirin, or aspirin alone. Also, there was no apparent increase in the risks of cancer-related deaths or cancer-related adverse events with long-term treatment.

The FDA is working with the manufacturers of clopidogrel to update the label to reflect the results of the mortality meta-analysis.

The recommendation is that patients should not stop taking clopidogrel or other antiplatelet medicines because doing so may result in an increased risk of thrombus and heart attacks. They suggest that patients talk to their health care professional if they have any questions or concerns about clopidogrel. Health care professionals should consider the benefits and risks of available antiplatelet medicines before starting treatment, the FDA recommends.

News from the EASD

Pesticides linked to risk of diabetes

Exposure to pesticides is associated with an increased risk of developing diabetes with different types of pesticides showing varying levels of risk, according to a study presented at this year’s annual meeting the European Association for the Study of Diabetes (EASD), Stockholm, Sweden.

Researchers from the University of Ioannina, Greece, and Imperial College London, analysed 21 studies on the association between pesticides and diabetes, covering 66,714 individuals (5,066 cases/ 61,648 controls). In almost all of the studies analysed, pesticide exposure was determined by blood or urine biomarker analysis.

The study found that exposure to any type of pesticide was associated with increased risk of any type of diabetes by 61%. In the 12 studies analysing only type 2 diabetes, the increased risk was 64% for those exposed to pesticides. For individual pesticides, increased risk was identified in association with exposure to chlordane, oxylchlordane, trans-nonachlor, DDT, DDE dieldrin, heptachlor and HCB.

Women with diabetes have higher risk of heart attack than men

Women with diabetes are more at risk than men of suffering from myocardial infarction and other complications as they age, according to new research presented at the meeting.

The study, carried out in the Regional Health Agency, Florence, Italy, was retrospective along a period of eight years (2005−2012) on a cohort of patients with diabetes living in Tuscany, Italy. It compared between genders the effect of age on diabetes-related excess risk of hospitalisation for acute myocardial infarction (AMI), ischaemic stroke (IS), and congestive heart failure (CHF).

The authors conclude: “In this cohort of Tuscan population, the excess risk of cardiovascular events linked with diabetes is significantly different between genders. With respect to AMI, [women with diabetes] are more disadvantaged, compared to [men with diabetes], with a gender driven ‘risk window’ for women which mostly opens around menopausal age (45 years onwards). Regarding IS and CHF, it opens later, in the postmenopausal age (55 years and over), and to a lesser extent. All this should focus attention on a timely, gender oriented, prevention of cardiovascular events in people with diabetes.”

…and are around 40% more likely to suffer ACS

Women with diabetes are around 40% more likely to suffer acute coronary syndromes (ACS) than men with diabetes, according to a meta-analysis of 19 studies containing almost 11 million patients, presented at the meeting.

The authors from Nanjing, China, examined case-control and cohort studies published between 1966 and 2014, with data for 10,856,279 individuals and at least 106,703 fatal and non-fatal ACS events. In patients with diabetes, women had a 38% increased risk of ACS.

The authors say: “Women with diabetes have a roughly 40% greater excess risk of ACS, compared with men with diabetes…We should avoid sexual prejudice in cardiovascular disease, take all necessary steps to diagnose it early, and control risk factors comprehensively to guarantee the most suitable treatments and best possible outcomes in female patients.”

Book review

Br J Cardiol 2015;22:133 Leave a comment
Click any image to enlarge
Authors:

The EHRA book of pacemaker, ICD, and CRT troubleshooting

EHRA bookEditors: Burri H, Deharo J-C, Israel C
Publisher: Oxford University Press, Oxford, 2015
ISBN: 978-0-19-872777-4 Price: £59.99

This case-based study guide for implantable device troubleshooting is composed of 70 ‘real-life’ cases involving pacemakers, implantable cardio-defibrillators (ICDs) and cardiac resynchronisation therapy (CRT) devices. It is aimed at all physicians and physiologists involved in the management of patients with implantable devices, and is the first in a series of specialist ‘handbooks’ produced by the European Heart Rhythm Association (EHRA). As such it particularly geared towards those sitting the EHRA affiliation examinations, although it would be equally useful to those planning to sit the British or American equivalents.

The cases are split into three sections (pacemakers 35 cases, ICDs 18 cases and CRT 17 cases) and ordered in sequence of increasing complexity, building on the knowledge acquired from previous cases. The electrograms (EGMs), device print-outs, and illustrations are well chosen and of very high reprographic quality, and the layout is not cramped as can sometimes be the case in such publications.

The questions all follow a multiple choice format, and the explanations to the answers are generally succinct yet sufficiently detailed; although in some cases where more than one answer is plausible it would be useful for the reader to also have a more detailed explanation of the reasons for the exclusion of the incorrect choices.

Many of the more complex areas are covered in good detail across several cases, although it is important for the reader to remember that this is designed to be a teaching aid rather than a reference text, and so should be used alongside a more comprehensive resource. For example inter-manufacturer algorithm differences are not always covered in detail, except in certain circumstances. Fundamentally, however, the key to attaining proficiency in this area is acquiring a good general understanding of the principles that underpin the programming of all devices.

These skills transcend manufacturer and model differences, and the authors lead the reader through these generic skills in a logical fashion, stressing the importance of a systematic approach to problem solving which is outlined in the introductory section. Helpfully the authors also point the reader towards a number of key publications which supplement further reading, and this book also contains a very useful glossary of commonly used annotations, and a number of good lists for revision purposes.

Overall, this is a very welcome addition to an increasingly important and complex area of cardiac care. The authors have produced a high quality study aid, which although not exhaustive, covers most of the key areas required for proficiency in device programming and troubleshooting, and as such can serve as an invaluable resource for either refreshing knowledge, or preparing for professional exams.

Dewi E Thomas 

Fellow in Cardiac Electrophysiology

James Cook University Hospital, Middlesbrough 

Book review

Br J Cardiol 2015;22:154 Leave a comment
Click any image to enlarge
Authors:

ESC textbook of cardiovascular imaging, 2nd edition

Screen shot 2015-11-25 at 14.52.21Editors: Zamorano JL, Bax J, Knuuti J, Sechtem U,
Lancellotti P, Badano L
Publisher: Oxford University Press, Oxford, 2015
ISBN: 978-0-19-870334-1 Price: £115

The second edition of the ESC textbook of cardiovascular imaging is a compendium of imaging expertise. The list of contributors alone should be enough to guarantee that there is something to learn for most involved in cardiology imaging.

The strengths are that it takes someone with a very limited knowledge of any of the individual modalities and walks them through the basics of how images are formed, through to making advanced diagnostic decisions. Some sections manage to seamlessly weave together fundamentals of clinical cardiology with European Society of Cardiology (ESC) guidelines and imaging characteristics, such as valvular heart disease. There is little overlap and much detail in the heart failure and cardiomyopathy sections that again encompasses teaching the topics themselves as well as the imaging detail. The more niche topics are particularly well written with truly multi-modality approaches. Examples include the distinction between restrictive and constrictive pericardial disease, and the imaging in cardiac resynchronisation sections.

Larger sections where there is more scope for competition between imaging modalities, sees the sales pitch of the experts. Assessment of coronary artery disease has the potential to end up as a battle to see who can quote the best sensitivity and specificity data, but actually allows the discerning reader to evaluate these whilst identifying limitations. The wealth of information, including documented percentage of at-risk myocardium and prognostication, is clear from the well-organised nuclear cardiology chapter, which clearly has the most historical data to validate. The cardiovascular magnetic resonance chapter provides a solid foundation for comparison in the functional assessment of coronary disease. Brief mention is made of the few head-to-head comparisons, and one has to reference back to the basics chapters to compare radiation doses.

Repetition is sometimes a problem. The modality-specific viability chapters each start off with their own description of the pathophysiology of stunning and hibernation. Whilst it is fascinating to see the different viewpoints, it is conceivable that so many descriptions of the same thing may leave the contiguous reader slightly frustrated if not confused. In addition, some areas spend a large amount of effort in unnecessary detail whilst omitting smaller but vital points. For example, the echocardiography section focuses on angles to obtain the ideal images − ‘a clockwise rotation of exactly 60° can be performed to visualise a correct 2-chamber’ − but has no disclaimer that morphology varies, especially in the elderly, or in fact that a protractor is necessary to perform an echo. In addition, not mentioning the importance of respiratory variation when obtaining images will seem bizarre to anyone who practices echocardiography.

The most glaring omission is the exceptionally brief and unenlightening description of imaging for percutaneous aortic valve replacement, a truly multi-modality phenomenon (and perhaps a reason for the oversight). This is even more notable when compared to the well-illustrated and lengthy section on percutaneous mitral valve clips.

Overall, despite some omissions and repetition there is much very useful information in this book and it gives an excellent account of how to assess, quantify and, in some cases, manage both common and rare cardiac conditions.

G Sunthar Kanaganayagam

Imaging Fellow

Hammersmith Hospital, London

Latest NICE guidelines on CRT and ICD devices in heart failure may significantly increase implant rates

Br J Cardiol 2015;22:155doi:10.5837/bjc.2015.041 Leave a comment
Click any image to enlarge
Authors:

In June 2014 the National Institute for Health and Care Excellence (NICE) released new guidelines (TA314) on the use of implantable cardioverter defibrillators (ICDs) and cardiac resynchronisation therapy devices (CRTs) in the management of heart failure. These guidelines replaced the previous TA95 and TA120 guidelines. We evaluated the potential impact on implant rates in our institution.

Clinical records of 396 consecutive patients were reviewed, with 100 patients included in the final analysis. Device indications and associated costs were calculated using both existing and new criteria.

NICE TA95/TA120 criteria recommended 37 devices: 20 ICDs, 9 CRTs with pacing (CRT-Ps), and 8 CRTs with defibrillator (CRT-Ds). The new NICE 2014 criteria recommended 97 devices: 56 ICDs, 7 CRT-Ps, and 34 CRT-Ds. Comparison of the new and old guidelines suggested a significant increase in total devices (p<0.0001). This corresponded primarily to an increase in ICDs and CRT-Ds, with an associated £661,708 increase in total spend (£407,205 increase per annum).

This study confirms the significant increase in ICDs and CRT-Ds indicated by NICE. This will have significant financial and workforce implications.

Continue reading Latest NICE guidelines on CRT and ICD devices in heart failure may significantly increase implant rates →

Impact of latest NICE guidelines on CRT and ICD implant rates

Br J Cardiol 2015;22:134–5doi:10.5837/bjc.2015.039 Leave a comment
Click any image to enlarge
Authors:

Cardiac implantable electronic devices (CIEDs) have an unquestionable evidence base in patients with reduced left ventricular ejection fraction (LVEF), already on optimal medical therapy. Implantable cardioverter defibrillators (ICDs) effectively treat ventricular arrhythmias, which account for up to 50% of mortality in patients with reduced LVEF.1 Likewise in appropriately selected patients, cardiac resynchronisation therapy (CRT) reduces hospitalisation rates, improves symptoms and prolongs life-expectancy.2

Dr Andrew J Turley (The James Cook University Hospital)
Dr Andrew J Turley (The
James Cook University Hospital)

Despite clear benefits, UK implant rates remain among the lowest in Europe, with wide regional variability seen. This variability is complex and poorly understood.3 One area of inconsistency is between local implementation of international and National Institute for Health and Care Excellence (NICE) guidance. In 2014, NICE released new guidance (TA314) on the use of ICDs and CRT that are significantly more inclusive than previous versions (TA95/TA120).4-6 There is no longer a need for QRS duration, evidence of non-sustained ventricular tachycardia (VT) or electrophysiological studies for ICD eligibility; furthermore, patients suffering non-ischaemic cardiomyopathy are now endorsed for device therapy. Within the CRT guidance, patients with atrial fibrillation (AF) and New York Heart Association (NYHA) class I–II symptoms are now included. This updated guideline has finally brought the UK in line with international societal guidance.7

In this issue, Mahendiran and colleagues examine the potential effect the ‘new’ NICE guidance may have on projected implant rates within a single-centre setting in the UK, and also the potential financial implications. The authors have used a dataset of 396 consecutive patients admitted to their hospital and referred to the heart failure service over a 19-month period. The records of the 143 patients with a LVEF ≤35% were further considered to determine their outcome post-discharge following a period of pharmacological optimisation. Of this group, 43 patients received no review following discharge. The remaining 100 records were analysed. Comparison of old and new NICE guidance suggested a significant increase in total device need. This corresponded primarily to a significant increase in CRT with defibrillation (CRT-D) implants (greatest absolute change seen in the ICD to CRT-D group). The population was older than most contemporary device trials, median age 79 years, with greater female representation (41%). The majority of patients were NYHA class II–III at follow-up and pharmacological use of angiotensin-converting enzyme inhibitors (ACEIs) and beta blockers was high.

The challenges

The authors conclude that NICE TA314 may significantly increase implant rates and this could have financial implications. Of course this is true. The new guidelines are more inclusive to the point that any patient with severe left ventricular systolic dysfunction (LVSD) has a potential device indication. The authors in their analysis confound matters by using ‘old’ NICE TA95 criteria, relaxed to include patients with non-ischaemic aetiologies of heart failure, and ‘old’ NICE TA120 criteria, relaxed to include patients with AF ‘as per local policies’. As such, the analysis is not a direct comparison between the two sets of NICE guidance, rather an analysis on local practice and implementation. As such, geographical biases are introduced.

For cost analysis, prices quoted in the NICE TA314 guidance were used. This is highly relevant. Based on average selling prices aggregated across all manufacturers of ICDs sold in the UK to the NHS in the financial year of 2011, the cost of a complete ICD, CRT with pacing (CRT-P) and CRT-D system was estimated at £9,692, £3,411 and £12,293, respectively. However, the unit cost, which includes unit overheads in addition to device costs (available from NICE on request), should be used in terms of financial modelling. The two prices differ considerably.

The cost impact of NICE TA314 is more complex than simply the historical cost of CIED systems. Device technology has advanced greatly since 2011. LV quadripolar-lead technology for CRT implants has improved implant success rates, reduced non-responder rates and the need for device revisions. In a recent UK multi-centre registry, all-cause mortality may also be lower in patents with quadripolar leads.8 Trials, such as MADIT RIT (Multicenter Automatic Defibrillator Implantation Trial – Reduce Inappropriate Therapy) and Advance III (Avoid Delivering Therapies for Nonsustained Arrhythmias in ICD Patients III) have tested new software algorithms and compared various therapy reduction programming strategies to reduce ICD therapies. These result in a consistent reduction in mortality.9-10 New CRT pacing algorithms have been introduced into clinical practice, e.g. multi-point pacing,11 although need long-term assessment in relation to clinical outcomes. Another significant advancement has been the introduction of remote technology to facilitate follow-up.12 Modern CIED have the ability to monitor patients outside of conventional clinical settings (e.g. at home). Features, such as trend analysis of physiological parameters, enable early detection of deterioration; potentially reducing the number of emergency visits, hospitalisations, and duration of hospital stays. Another factor vital in any cost-effectiveness analysis.

These advancements were not analysed in the NICE cost-effectiveness model and it may be, with modern technology and programming strategies, the prognostic benefit of CIED is greater than initially seen in the landmark trials.

Finally, this is not the first time authors report greater than anticipated increases in device indications following the release of new guidance. Plummer and colleagues reported that ICD indications were three times greater than anticipated by NICE following the release of TA95.13 While this is true, clinical indications do not equate to implants for many reasons. Through shared decision-making, some patients will specifically decline device therapy while others may be too sick to benefit.14 Review of the UK device survey shows that ICD implant rates in England have steadily increased over the last 7–8 years with no significant jump after the introduction of a major guideline change.15

Conclusion

While the latest NICE guidelines on the use of CIEDs in patients with heart failure are warmly welcomed, and will hopefully lead to a greater number of device implantations, barriers remain that will limit the translation of current guidance into daily practice. It is clear that education is required to highlight device indications, however, the biggest difficulty we currently face is that we do not fully understand the reasons for disparity in implantation rates within the UK.

Conflict of interest

AJT has received financial reimbursement to attend international meetings from Medtronic, St. Jude Medical and Boston Scientific.

Editors’ note

See also the article by Mahendiran et al. in this issue.

References

1. Adabag AS, Luepker RV, Roger VL, Gersh BJ. Sudden cardiac death: epidemiology and risk factors. Nat Rev Cardiol 2010;7:216–25. http://dx.doi.org/10.1038/nrcardio.2010.3

2. Goldenberg I, Kutyifa V, Klein HU et al. Survival with cardiac-resynchronization therapy in mild heart failure. N Engl J Med 2014;370:1694–701. http://dx.doi.org/10.1056/NEJMoa1401426

3. McComb JM, Plummer CJ, Cunningham MW, Cunningham D. Inequity of access to implantable cardioverter defibrillator therapy in England: possible causes of geographical variation in implantation rates. Europace 2009;11:1308–12. http://dx.doi.org/10.1093/europace/eup264

4. National Institute for Health and Care Excellence. Implantable cardioverter defibrillators and cardiac resynchronisation therapy for arrhythmias and heart failure (review of TA95 and TA120). London: NICE, 2014. Available from: http://guidance.nice.org.uk/ta314

5. National Institute for Health and Care Excellence. NICE Technology Appraisal Guidance 95. Implantable cardioverter defibrillators for arrhythmias. London: NICE, 2006. Available from: https://www.nice.org.uk/guidance/ta95

6. National Institute for Health and Care Excellence. NICE technology appraisal guidance 120. Cardiac resynchronisation therapy for the treatment of heart failure. London: NICE, 2007. Available from: https://www.nice.org.uk/guidance/ta120

7. Epstein AE, DiMarco JP, Ellenbogen KA et al. 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation 2013;127:e283–e352. http://dx.doi.org/10.1161/CIR.0b013e318276ce9b

8. Behar JM, Bostock J, Zhu Li AP et al. Cardiac resynchronization therapy delivered via a multipolar left ventricular lead is associated with reduced mortality and elimination of phrenic nerve stimulation: long-term follow-up from a multicenter registry. J Cardiovasc Electrophysiol 2015;26:540–6. http://dx.doi.org/10.1111/jce.12625

9. Moss AJ, Schuger C, Beck CA et al. Reduction in inappropriate therapy and mortality through ICD programming. N Engl J Med 2012;367:2275–83. http://dx.doi.org/10.1056/NEJMoa1211107

10. Kloppe A, Proclemer A, Arenal A et al. Efficacy of long detection interval implantable cardioverter-defibrillator settings in secondary prevention population: data from the Avoid Delivering Therapies for Nonsustained Arrhythmias in ICD Patients III (ADVANCE III) trial. Circulation 2014;130:308–14. http://dx.doi.org/10.1161/CIRCULATIONAHA.114.009468

11. Pappone C, Calovic Ž, Vicedomini G et al. Improving cardiac resynchronization therapy response with multipoint left ventricular pacing: twelve-month follow-up study. Heart Rhythm 2015;12:1250–8. http://dx.doi.org/10.1016/j.hrthm.2015.02.008

12. Slotwiner D, Varma N, Akar JG et al. HRS Expert Consensus Statement on remote interrogation and monitoring for cardiovascular implantable electronic devices. Heart Rhythm 2015;12:e69–e100. http://dx.doi.org/10.1016/j.hrthm.2015.05.008

13. Plummer CJ, Irving JR, McComb JM. The incidence of implantable cardioverter defibrillator indications in patients admitted to all coronary care units in a single district. Europace 2005;7:266–72. http://dx.doi.org/10.1016/j.eupc.2005.01.006

14. Barsheshet A, Moss AJ, Huang DT, McNitt S, Zareba W, Goldenberg I. Applicability of a risk score for prediction of the long-term (8-year) benefit of the implantable cardioverter-defibrillator. J Am Coll Cardiol 2012;59:2075–9. http://dx.doi.org/10.1016/j.jacc.2012.02.036

15. British Heart Rhythm Society Audit Group. National audit of cardiac rhythm management devices 2013–2014. London: BHRS, 2014. Available from: http://www.devicesurvey.com/

Barriers to cardiac device innovation

Br J Cardiol 2015;22:136doi:10.5837/bjc.2015.040 Leave a comment
Click any image to enlarge
Authors:

The UK population is getting older and the amount of cardiovascular disease is increasing significantly, fuelled by a steep rise in the incidence of obesity and diabetes. Heart failure is increasing in incidence because of improved survival rates following myocardial infarction and more effective treatments, with an estimated 500,000 sufferers.1 People with heart failure are more at risk of sudden cardiac death and many can benefit from cardiac devices such as implantable cardioverter defibrillators (ICDs) and cardiac resynchronisation devices (CRT-D/Ps). This increasing need was recognised by the National Institute of Health and Care Excellence (NICE) in 2014 with the publication of the revised guidelines for the use of such devices.2 Nevertheless, the UK remains well below the European average for ICD implants, although is improving in terms of CRT devices;3 the latter due to a higher than average implant rate of CRT pacemakers. However, the rate of implantation of all high-energy devices (ICD + CRT-D) is only slightly more than half the European average.

Dr Nick Linker (President, British Heart Rhythm Society)
Dr Nick Linker (President, British Heart Rhythm Society)

Despite the need to implant more devices in patients and to develop new, innovative, devices there remain major obstacles. The recent report from the Cardiovascular Round Table4 highlights some of these barriers. Delays in implementation of guidelines, and in dissemination of new devices, vary throughout Europe, and are related to a number of factors such as funding, complex R&D lifecycles and regulatory issues. The cumulative result is inconsistent delivery both across Europe and within the UK. In Germany, hospitals can access an innovation fund set up by health insurers to exploit innovative techniques that offer positive outcomes. This enabled transcatheter aortic valve implantation (TAVI) to be available within one year of the devices receiving a CE mark. Implementation of innovative technology in the UK is currently through the Commissioning through Evaluation process, which is, at present, evaluating three cardiology procedures: percutaneous mitral valve leaflet repair (using MitraClip) for mitral regurgitation in patients with heart failure; patent foramen ovale closure for the prevention of recurrent stroke; and left atrial appendage occlusion for the prevention of stroke.5 This process has taken almost two years to set up and will not report until 2017, at the earliest, at which point a decision will be made by NHS England as to whether to commission these procedures. While there are good scientific and economic reasons to develop such a system of evaluation in the absence of large-scale trial data, it does mean that this process could result in UK patients not having access to these technologies, which are already available in other European countries.

The Cardiovascular Round Table argues that an inefficient and inconsistent approach to the introduction and funding of innovative therapies poses a genuine threat to future development, with anecdotal evidence that some companies are already cutting R&D budgets as a response to delays in adoption and low take-up rates of technology, such as TAVI and percutaneous mitral valve repair. They argue for greater involvement of National Societies, such as the British Heart Rhythm Society (BHRS), British Cardiovascular Intervention Society (BCIS), British Cardiovascular Society (BCS) and others with healthcare providers and, furthermore, that the European Commission should establish timescales for the allocation of national funding for new procedures. While it is unlikely that the European Commission will have a significant influence on the NHS, it is important that clinicians, backed by their National Societies, continue to engage and push to get the funding and support to develop these procedures.

Conflict of interest

NJL has received consultancy fees and research grants from Medtronic, St Jude Medical and Boston Scientific.

References

1. British Heart Foundation Centre on Population Approaches for Non‐Communicable Disease Prevention. Cardiovascular disease statistics 2014. London: British Heart Foundation, 2014. Available from: https://www.bhf.org.uk/~/media/files/publications/research/bhf_cvd-statistics-2014_web_2.pdf

2. National Institute for Health and Care Excellence. Implantable cardioverter defibrillators and cardiac resynchronisation therapy for arrhythmias and heart failure. London: NICE, 2014. Available from: https://www.nice.org.uk/guidance/ta314/resources/guidance-implantable-cardioverter-defibrillators-and-cardiac-resynchronisation-therapy-for-arrhythmias-and-heart-failure-review-of-ta95-and-ta120-pdf

3. British Heart Rhythm Society Audit Group. National audit of cardiac rhythm management devices 2013–2014. London: BHRS, 2014. Available from: http://www.devicesurvey.com/

4. Pinto F, Fraser AG, Kautzner J et al. Barriers to cardiovascular device innovation in Europe. Eur Heart J 2015;published online. http://dx.doi.org/10.1093/eurheartj/ehv275

5. NHS England. NHS Commissioning: Commissioning through Evaluation. Available at: http://www.england.nhs.uk/commissioning/spec-services/npc-crg/comm-eval/

Healthcare professional’s guide to cardiopulmonary exercise testing

Br J Cardiol 2015;22:156doi:10.5837/bjc.2015.042 Leave a comment
Click any image to enlarge
Authors:

Cardiopulmonary exercise testing (CPEX) is a valuable clinical tool that has proven indications within the fields of cardiovascular, respiratory and pre-operative medical care. Validated uses include investigation of the underlying mechanism in patients with breathlessness, monitoring functional status in patients with known cardiovascular disease and pre-operative functional state assessment. An understanding of the underlying physiology of exercise, and the perturbations associated with pathological states, is essential for healthcare professionals to provide optimal patient care. Healthcare professionals may find performing CPEX to be daunting, yet this is often due to a lack of local expertise and guidance with testing. We outline the indications for CPEX within the clinical setting, present a typical protocol that is easy to implement, explain the key underlying physiological changes assessed by CPEX, and review the evidence behind its use in routine clinical practice. There is mounting evidence for the use of CPEX clinically, and an ever-growing utilisation of the test within research fields; a sound knowledge of CPEX is essential for healthcare professionals involved in routine patient care. 

Continue reading Healthcare professional’s guide to cardiopulmonary exercise testing →