In brief

Br J Cardiol 2016;23:53–4 Leave a comment
Click any image to enlarge
Authors:

NICE recommendations for PCSK9 inhibitors

The National Institute for Health and Care Excellence (NICE) has published recommendations supporting the use of two new lipid-lowering agents – both PCSK9 inhibitors, which inhibit the body’s natural system for eliminating low-density lipoprotein cholesterol (LDL-C).

A Final Appraisal Determination (FAD) has been published for evolocumab (Repatha®, Amgen) recommending it be used alone or in combination with other cholesterol-lowering therapies, for several types of patients at particularly high risk of cardiovascular events with persistently high cholesterol despite maximal tolerated lipid-lowering therapy.  The NICE recommendation is based on a positive assessment of evolocumab’s clinical and cost effectiveness.

A FAD has also been published for alirocumab (Praluent®, Sanofi) recommending it as a treatment option for people who have raised levels of LDL-C, and who are at significantly high risk of a heart attack or stroke.

In response to the news of the two NICE FADs for alirocumab and evolocumab, Professor Peter Weissberg (Medical Director, British Heart Foundation) said: “The new PCSK9 inhibitors approved for use by NICE are a new and exciting way to reduce harmful cholesterol levels. However, because their long-term safety is still unknown, and they are yet to show reduced risk of heart attack, their use is currently restricted to patients with dangerously high cholesterol levels despite treatment with statins”.

“This new class of drugs is undergoing intensive clinical investigation. Guidelines are likely to change in the future as more information is revealed surrounding their safety and effectiveness,” he concluded. The FADs are available at www.nice.org.uk

Selexipag now available for pulmonary hypertension

Actelion Pharmaceuticals have announced that selexipag (Uptravi®), a selective IP prostacyclin receptor agonist, has been granted marketing authorisation for the long-term treatment of pulmonary arterial hypertension (PAH) in the European Union by the European Commission.

PAH is a chronic, life-threatening disorder affecting between 6,000–7,000 people in the UK. Selexipag has been licensed for the long-term treatment of PAH in adult patients with WHO functional class (FC) II-III, either as a combination therapy in patients insufficiently controlled with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor, or as monotherapy in patients who are not candidates for these therapies.

Professor Sean Gaine (Consultant Respiratory Physician, Mater Misericordiae Hospital, Dublin, Ireland) commented: “For many years we have known that the prostacyclin pathway is a key target in PAH treatment, a pathway that has been underused largely due to the route of administration of the existing therapies.  An innovative, oral treatment, supported by long-term outcome results will allow us to offer convenient triple combination therapy regimens that target these three established treatment pathways. With this approach we not only aim to delay disease progression but we are looking for long-term benefits for our patients. Uptravi is a treatment option that could really change the way we treat PAH patients,” he concluded.

Poor patient warfarin knowledge may increase risk of deadly side effects 

Patients have poor knowledge of warfarin, which may increase their risk of serious side effects, according to research recently presented at EuroHeartCare 2016 by Dr Kjersti Oterhals (nurse researcher, Haukeland University Hospital, Bergen, Norway).

The study included 404 patients with aortic stenosis who were taking warfarin. Nearly two-thirds (63%) took warfarin because they had a mechanical heart valve to treat aortic stenosis and 24% took the drug because they had atrial fibrillation. Patients were 68 years old on average and 70% were men. Patients received a postal questionnaire with 28 multiple-choice questions about warfarin. They answered 18 questions correctly on average but 22% gave correct answers on less than half of the questions. Questions with the least correct answers concerned food and drug interactions and when to call a doctor.

When asked which of the following foods would interfere with warfarin: celery, carrot, coleslaw or green beans, just 25% correctly said coleslaw and most patients answered green beans.

“Patients often think green vegetables have the most vitamin K but that’s not true,” said Dr Oterhals. “Brassica vegetables such as cabbage, broccoli and cauliflower are rich sources. Patients do not have to avoid these foods but they should eat an equal amount every week because the vitamin K will decrease their international normalised ratio (INR) and put them at increased risk of thrombosis or embolism. Patients who like to eat a lot of vitamin K-containing foods can take a higher warfarin dosage, but they need to be consistent.”

Tesco stores have 900 defibrillators

The Arrhythmia Alliance has announced that every Tesco shopper is now ‘HeartSafe’ with the placement of over 900 automated external defibrillators (AEDs) in stores across the UK, supported by the Defibs Save Lives campaign.

This follows the launch of the Arrhythmia Alliance manifesto, ‘Now Is The Time… for Action to Save Lives,’ which called for greater awareness and placement of public access AEDs in communities to increase the chances of survival from a sudden cardiac arrest (SCA).

On its own, cardiopulmonary resuscitation (CPR) can save up to 10% of SCA victims but when an AED is used as well, this can increase survival to over 50% in people with a shockable heart rhythm. Every minute without defibrillation decreases survival by 10%.

New editorial board members

We are delighted to announce two new members to our board. Professor Andrew L Clark is Chair of Clinical Cardiology and Honorary Consultant Cardiologist, Castle Hill Hospital, Cottingham, Hull. He is Chair of the British Society for Heart Failure, and is a member of the working groups for Heart Failure and Cardiac Rehabilitation and Exercise Physiology in the European Society of Cardiology. Dr Robby Rakhit is Consultant Interventional Cardiologist and Honorary Senior Lecturer, Royal Free Hospital, London. His clinical Interests include complex PCI, primary PCI, intracoronary imaging and physiology, and HIV, diabetes and coronary disease.

MHRA reports QRISK®2 error calculations

The Medicines and Healthcare products Regulatory Agency (MHRA) has highlighted an issue with the QRISK®2 Calculator in SystmOne, supplied by the company TPP. For some patients it has produced incorrect results when assessing the potential risk of cardiovascular disease. For a proportion of patients the potential of heart disease could have been over or understated.

The MHRA is working with TPP to resolve the issue. For more information, contact Mike Dykes at the MHRA ([email protected]).

Preparing patients for cardiothoracic surgery 

Private healthcare provider BUPA has recently joined forces with the Society for Cardiothoracic Surgery (SCTS) to produce a hub of information for both medical professionals and the general public. The aim is to help consultants and cardiothoracic nurses to deliver a better service to their patients; and for this to be somewhere people can go to learn more about heart surgery.

The mini website provides clear and comprehensive information around having heart surgery and contains everything from short films with surgeons, factsheets on how patients can prepare for surgery and thorough information around aortic valve surgery (AVR). Some of the information is available as handy little factsheets and checklists for both medics and patients to use.

You can view the hub here: http://www.bupa.co.uk/SCTS-heart-surgery

Philips e-health initiative across Europe

The health technology company Phillips has announced that it is leading a healthcare initiative with a consortium of European healthcare regions, companies, universities and hospitals to deliver the first large-scale care, coordination and telehealth programme in the European Union (EU) to support tens of thousands of people living with chronic conditions.

The three-year ACT Scale programme will collect and analyse the health outcome and economic impact data for large populations of chronic patients and elderly people. The aim is to develop, test and consolidate ‘best practice’ care coordination and telehealth programmes that can be replicated and successfully rolled out across the EU. The programme aims to reach more than 75,000 patients (including more than 4,000 patients in the UK), the Netherlands, Spain and Denmark by 2019.

‘Home Assist’ telecare service launched

A new telecare service called ‘Home Assist’ is being trialled by Boots UK in collaboration with Tunstall Healthcare. Currently 3.5 million people aged 65 years and over live alone in UK with more than half of these being over 75 years old.

The 24/7 remote monitoring service, offers three different service packages that can be customised according to the key needs of the user, including remote monitoring for falls, smoke detection and risk of hypothermia. All three services alert a member of the support team as soon as help is needed. By pressing a button on the pendant, the user can talk to the support team through the speaker on the base unit hub (the pendant can connect to the hub from a distance of up to 50 metres).

The ‘Home Assist’ service is installed by professional engineers without additional charge. The initial trial of the service started in February. More information can be found at http://www.homeassistuk.com

Yoga improves quality of life in patients with atrial fibrillation

Screen shot 2016-06-02 at 11.26.29Yoga improves quality of life in patients with paroxysmal atrial fibrillation (AF), according to research published in the European Journal of Cardiovascular Nursing (doi: 10.1177/1474515116637734).

Heart rate and blood pressure also decreased in patients who did yoga.

“Many patients with paroxysmal AF can’t live their lives as they want to…because they are afraid of an AF episode occurring,” according to Maria Wahlström (nurse and PhD candidate, Sophiahemmet University and the Karolinska Institute, Stockholm, Sweden).

The current study included 80 patients with paroxysmal AF who were randomised to yoga or a control group that did not do yoga. Both groups received standard treatment with medication, cardioversion and catheter ablation as needed. Yoga was performed for one hour, once a week, for 12 weeks in the hospital with an experienced instructor. The yoga programme included light movements, deep breathing, and meditation.

Ms Wahlström said: “We found that patients who did yoga had a better quality of life, lower heart rate and lower blood pressure than patients who did not do yoga. It could be that the deep breathing balances the parasympathetic and sympathetic nervous system, leading to less variation in heart rate. The breathing and movement may have beneficial effects on blood pressure.”

Correspondence: Nicorandil, antithrombotic drugs, and non-variceal upper gastrointestinal bleeding

Br J Cardiol 2016;23:56 Leave a comment
Click any image to enlarge
Authors:

Dear Sirs,

Of the serious complications of gastrointestinal ulcers (bleeding, perforation, obstruction, and sometimes death), non-variceal upper gastrointestinal bleeding (NVUGIB) remains the commonest. These days it is mostly seen in association with the use of antithrombotic drugs (ATDs), particularly low-dose aspirin (75–325 mg/day), given for vascular protection.1

Nicorandil is a vasodilator that acts as a nitrate and K+ATP channel agonist. It is used in many countries worldwide and is often added to ATDs in the management of angina. In light of some case reports, its manufacturer and the medicines advisors and regulatory agencies have issued cautions that it can cause mucosal ulcers, perforation and bleeding, and that these might be worse in users of aspirin.2,3 We therefore investigated the possibility that NVUGIB is more severe in patients using ATDs plus nicorandil than ATDs alone.

In an observational and retrospective analysis, patients presenting to our institution during 2010–2014 with NVUGIB and using ATDs plus nicorandil (n=59) were compared to those using ATDs alone (controls; n=1,056). We compared haemoglobin level, Blatchford UGIB risk score,4 composite endoscopy score (covering erosive and ulcer lesions in the oesophagus, stomach and duodenum),5 need for blood transfusion, length of hospital admission, and 30-day mortality. NVUGIB comprised haematemesis and/or melena in the absence of portal hypertensive gastropathy, oesophageal or gastric varices.1 ATDs included low-dose aspirin, clopidogrel, dipyridamole, warfarin and heparin. The work was approved by the institutional Clinical Governance Team.

Table 1. Outcomes of NVUGIB and characteristics of patients taking ATDs plus nicorandil versus those taking ATDs alone
Table 1. Outcomes of NVUGIB and characteristics of patients taking ATDs plus nicorandil versus those taking ATDs alone

The outcomes of NVUGIB and the characteristics of patients using ATDs alone versus those using ATDs plus nicorandil are shown in table 1. Age and haemoglobin are shown as mean (SD); Blatchford score, endoscopic score and length of admission as median (interquartile range); and binary variables as number (percentage). The final column shows differences between groups (nicorandil minus control) with 95% confidence intervals. All differences were statistically insignificant (P>0.05, Student’s t, Mann-Whitney and Fisher’s exact tests as appropriate). Patients taking ATDs plus nicorandil were well matched demographically with controls taking ATDs alone. The confidence intervals place a modest upper limit on any exacerbation of NVUGIB by nicorandil as manifested by reduced haemoglobin and increased need for transfusion. The intake of nicorandil does not seem to worsen the severity or the outcomes of NVUGIB.

While acknowledging the limitations of observational analysis, these findings do not justify discontinuing nicorandil in patients with angina and presenting with NVUGIB while taking ATDs.

Conflict of interest

None declared.

Ali S Taha 
Consultant and Senior Lecturer in Gastroenterology
University Hospital Crosshouse, Kilmarnock, and The School of Medicine, University of Glasgow
([email protected])

Caroline McCloskey  
Specialist Nurse Practitioner
University Hospital Crosshouse, Kilmarnock

Wilson J Angerson   
Senior Statistician
The School of Medicine, University of Glasgow

References

1. Taha AS, Kelly C, McCloskey C, et al. Upper gastrointestinal bleeding in hospital inpatients: the role of antithrombotic drugs. Postgrad Med J 2014;90:429–33. http://dx.doi.org/10.1136/postgradmedj-2013-132231 

2. Harman C. Nicorandil use restricted over ulceration risk. MIMS 2015. http://www.mims.co.uk/nicorandil-use-restricted-ulceration-risk/cardiovascular-system/article/1373133 (accessed 5 January 2016).

3. Robinson M. Nicorandil is now firmly second line. Prescribing advice for GPs – an NHS prescribing advisers’ blog. http://www.prescriber.org.uk/2015/11/nicorandil-now-firmly-second-line/ (accessed 5 January 2016).

4. Taha AS, Angerson WJ, Knill-Jones RP, et al. Clinical outcome in upper gastrointestinal bleeding complicating low-dose aspirin and antithrombotic therapy. Aliment Pharmacol Ther 2006;24:633–6. http://dx.doi.org/10.1111/j.1365-2036.2006.03017.x 

5. Taha AS, McCloskey C, Craigen T, et al. Antithrombotic versus ulcer effects in non-variceal bleeding in users of antithrombotic drugs. Gut 2014;63:A45–A46. http://dx.doi.org/10.1136/gutjnl-2014-307263.93

Book review: Upon a trailing edge

Br J Cardiol 2016;23:81 Leave a comment
Click any image to enlarge
Authors:

Author: M Joy

EHRA bookPublisher: Matador, 2015
ISBN: 9781784624729 Price: £17.99

The author describes this as a story about aviation, its risks and the heart of the pilot. It is a story told extremely well from a unique personal perspective and should have wide appeal. It is principally an autobiography charting the author’s life in aviation and cardiology, and the interface between them that deals with the impact of cardiovascular disease on a pilot’s fitness to fly. It also includes a brief history of powered flight, insights into human factors and the quantification and containment of risk, as well as some entertaining travel writing, as the author recounts numerous trips abroad in the course of his work.

Early chapters describe his post-war childhood and school days, including early flying experience in the Cadet Corps and a flying scholarship with the RAF section, leading to the award of the author’s flying licence in a Tiger Moth. After qualifying in medicine, he resumed his flying activities alongside a career in cardiology, owning and flying several light aircraft, achieving nearly 1,000 hours as pilot in command, along with night, instrument and twin-engine ratings.

This experience equipped him well to become the first cardiologist appointed to the UK Civil Aviation Authority (CAA) soon after the fatal 1972 crash of BEA Trident G-ARPI (Papa India) shortly after take-off from Heathrow. The accident was caused by the pilot suffering incapacitation due to myocardial infarction, compounded by numerous operational and human factors. It prompted a greater emphasis on Crew Resource Management (now increasingly adopted in healthcare), as well as the introduction of training in the recognition and management of pilot incapacitation, which has greatly reduced the risk of an accident arising from medical causes in multi-crew operations.

The accident inquiry also recommended the centralised scrutiny of aircrew electrocardiograms (ECGs), which was the author’s initial role at the CAA but this was soon extended to the cardiological assessment of aircrew and membership of the Medical Advisory Panel, set up to provide specialist advice to the Chief Medical Officer. As consultant to the CAA for 38 years, the author strove to put the cardiovascular assessment of aircrew on an evidence-based scientific footing. This included the organisation of two UK and two European Workshops in Aviation Cardiology between 1982 and 1998 and the drafting of European and International standards for cardiovascular fitness to fly.

Later chapters describe the author’s extensive experience as a private pilot traversing Europe (often to attend professional meetings, including those of the European Society of Cardiology) in a variety of aeroplanes and weather conditions. The understanding of the operational environment afforded by such adventures clearly facilitated the informed assessment of aircrew with cardiological problems in a regulatory context, as well as commanding the respect of those being assessed.

In closing, the author offers some specific suggestions on operational issues to further improve aviation safety and counsels strongly against the proposed outsourcing of medical services by the regulator – if his forthright views in that regard generate some wake turbulence, that may be no bad thing. To quote the author, “safety is a fragile flower”. He has done much to cultivate it, and his insights should command the attention of those charged with its preservation and enhancement.

The book is engaging and discursive in style but there is sufficient technical detail on medical, aeronautical and regulatory issues. There are historical insights, innumerable illustrative examples of aviation accidents and the lessons to be learned from them, evocative descriptions of some remarkable people and an abundance of entertaining anecdotes. This is a book for the curious and it does not disappoint.

William D Toff

Senior Lecturer in Cardiology

Department of Cardiovascular Sciences

University of Leicester

Leicester, LE1 7RH

Growing need for trainees in adult congenital heart disease in the UK

Br J Cardiol 2016;23:49–50doi:10.5837/bjc.2016.014 Leave a comment
Click any image to enlarge
Authors:

Deaths from congenital heart disease in childhood have fallen 83% in the last 25 years.1 This dramatic change has led to a significant increase in the numbers of adults with congenital heart disease (ACHD) requiring care, and prevalence is not expected to plateau until 2050.2 Even patients with extremely complex pathophysiology are now expected to survive well into adult life, and will have significantly higher rates of utilisation of all hospital services than the general population.3,4 

Screen shot 2016-04-19 at 11.19.34The consultant workforce in ACHD in the UK is small, and faces substantial shortages. With very few trainees currently opting to train in ACHD, the workforce will fall even further behind, as patient numbers and complexity increase.5

A career in congenital heart disease – what does it offer the cardiologist?

A career in ACHD offers a professional lifetime of endless variation. In outpatients, you will see patients with infinitely variable anatomy and often complex physiology, over the course of many years, and through many medical and non-medical lifetime events. Fewer patients need inpatient care, and, when required, this is usually due to an acute arrhythmia, endocarditis or heart failure, cardiac or non-cardiac surgery or percutaneous intervention. Use of multi-modality imaging is an integral part of daily practice.

The ACHD cardiologist has to be something of a ‘generalist’, but this does not preclude further sub-specialisation within ACHD in intervention, imaging, electrophysiology and pacing, heart failure and end-of-life care, transition, pregnancy and pulmonary hypertension.

ACHD cardiologists work as part of a multi-disciplinary team alongside cardiac surgeons, specialist nurses, cardiac physiologists, physiotherapists, and psychologists.

For those with an academic orientation, there are research opportunities galore. Largely, thus far, an untapped resource, almost every question regarding ongoing care and management is unanswered, a dream for every budding academic.

If you choose a career in ACHD, one thing you will not be, is bored!

Training

Core curriculum training – recent changes to curriculum

The general cardiologist is increasingly likely to encounter an acutely unwell ACHD patient while on-call. All cardiology trainees must be equipped with the knowledge-base and skills to manage the initial acute presentation, and know when to involve the specialist centre. Changes have been made to the core curriculum to ensure a broad knowledge-base.6 Trainees are encouraged to complete a free online core curriculum course,7 or attend an equivalent face-to-face course, and a dedicated two-week clinical attachment in a specialist surgical centre is recommended. This should take place as early as possible during ST3/4/5 to allow time for interested trainees to explore options for sub-specialty training. Trainees are also now required to upload a checklist to their e-portfolio as supportive evidence that they have achieved the basic competencies across the full range of conditions required to practise safely as a general cardiologist.

Sub-specialty training

Prior to 2002, exposure to ACHD patients was piecemeal during general cardiology training, and sub-specialty training was a scarce resource.

In 2002, five national sub-specialty (ST6/7) ACHD training posts were established around already active centres in London, Southampton, Bristol, Birmingham and Leeds. These posts are advertised nationally and are open to anyone with a National Training Number (NTN) in either Adult or Paediatric Cardiology. Increasingly, there are also opportunities to pursue sub-specialty training in ACHD in a number of other centres via local arrangements. ACHD training at ST6/7 can consist of a module of four units (two years) – providing training in all aspects of ACHD for those aiming to work in a specialist centre, or two modules of ACHD (one year) can be combined with two modules in another sub-specialty, such as advanced imaging or heart failure, for those wishing to work as a consultant with an interest in ACHD.

Barriers to training

The numbers of applicants for sub-specialty ACHD training posts are small, and posts are at times left unfilled, increasing concerns regarding future manpower provision.

There appear to be a number of bars to trainees pursuing careers in ACHD. Some trainees are concerned that ACHD is ‘too difficult’ for them. Any trainee with a good understanding of cardiac physiology will come to realise quickly that ACHD is a science rather than a dark art, and once familiar with the subject, it is no more challenging than any other area in cardiology.

The five national sub-specialty posts are relatively thinly geographically spread and may only be advertised once every two years; it is easy for the interested trainee committed to one geographical area to miss out, simply by adverse timing. Negotiating through the out-of-programme-training (OOPT) process can be somewhat daunting if applying from out of region. Some individuals are counselled against ACHD sub-specialty training by well-meaning advisors who mistakenly believe ACHD is over-subscribed. Furthermore, some trainees are deterred because the geographic options open to them at the time of consultant appointment are likely to be more limited than for more general cardiology posts.

National structure of care and employment opportunities

The recent prolonged period of scrutiny of congenital heart services appears to be nearing conclusion. A new model and standards of care have been agreed by NHS England.8 The recommended structures rely heavily on implementation of regional and supra-regional clinical networks, with (usually) one specialist ACHD surgical centre (Level 1) acting as the central hub. Specialist ACHD centres (Level 2) aiming to provide the same level of expertise as Level 1 centres, require a significant commitment to ACHD from at least two cardiologists, but do not provide surgery or intervention. There may be a significant expansion in local ACHD centres (Level 3), which will require cardiologists with an interest in ACHD to work alongside cardiologists from the specialist ACHD centre.

Conclusion

ACHD offers a uniquely interesting and challenging career in cardiology, with opportunities to further super sub-specialise in particular areas of interest. We hope recent changes to the curriculum will expose trainees to an enhanced experience of ACHD earlier in their training, allowing them more time to arrange sub-specialty training in ST6/7.

Over the next few years there will need to be a significant increase in consultant workforce to cope with the rapidly increasing population, and also to fulfil the requirements of the NHS England standards of care. This includes specialist ACHD cardiologists (with at least two years ACHD experience in ST6/7) to work in Level 1 centres, but also cardiologists with expertise and interest in ACHD to work in Level 2 and 3 centres.

If you are interested in pursuing a career in ACHD, please contact the authors or the ACHD cardiologists at your local centre for more advice.

Conflict of interest

None declared.

References

1. Townsend N, Bhatnagar P, Wickramasinghe K et al. Children and young people statistics 2013. British Heart Foundation: London, 2013.

2. Benziger CP, Stout K, Zaragoza-Macias E, Bertozzi-Villa A, Flaxman AD. Projected growth of the adult congenital heart disease population in the US to 2050: an integrative systems modelling approach. Popul Health Metr 2015;13:29. http://dx.doi.org/10.1186/s12963-015-0063-z

3. Van der Bom T, Mulder BJ, Meijboom FJ et al. Contemporary survival of adults with congenital heart disease. Heart 2015;101:1989–95. http://dx.doi.org/10.1136/heartjnl-2015-308144

4. Mackie AS, Pilote L, Ionescu-Ittu R, Rahme E, Marelli AJ. Health care resource utilization in adults with congenital heart disease. Am J Cardiol 2007;99:839. http://dx.doi.org/10.1016/j.amjcard.2006.10.054

5. Holdsworth D. Changes and challenges in cardiology training. BMJ Careers published online, 8 November 2012. Available from: http://careers.bmj.com/careers/advice/Changes_and_challenges_in_cardiology_training

6. Joint Royal Colleges of Physicians Training Board. Cardiology: about the specialty. Available at: http://www.jrcptb.org.uk/specialties/cardiology

7. Adult Congenital Heart Disease Learning Center. Available at: http://www.achdlearningcenter.org

8. NHS England. New congenital heart disease review: final report. Available from: https://www.england.nhs.uk/wp-content/uploads/2015/07/Item-4-CHD-Report.pdf

Triple-valve infective endocarditis

Br J Cardiol 2016;23:65–7doi:10.5837/bjc.2016.015 Leave a comment
Click any image to enlarge
Authors:

Despite the significant improvements in both diagnostic and therapeutic procedures in recent years, infective endocarditis (IE) remains a medical challenge due to poor prognosis and high mortality. Echocardiographically, the majority of the patients demonstrate vegetations on a single valve, while demonstration of involvement of two valves occurs much less frequently; triple-valve involvement is extremely rare. Reported operative mortality after triple-valve surgery is high and ranges between 20% and 25%. 

Surgical treatment is used in approximately half of patients with IE because of severe complications. Reasons to consider early surgery in the active phase, i.e. while the patient is still receiving antibiotic treatment, are to avoid progressive heart failure and irreversible structural damage caused by severe infection, and to prevent systemic embolism. Prognosis in IE is influenced by four main factors: characteristics of the patient, the presence or absence of cardiac and non-cardiac complications, the infecting organism, and echocardiographic findings. Prognosis of right-sided native valve endocarditis is relatively good, with an in-hospital mortality rate of about 10%.

We present a case of a young man with triple-valve endocarditis followed by a brief review of the literature.

Introduction

Figure 1. Chest X-ray (antero-posterior projection) demonstrating a septic lesion (thick arrow)
Figure 1. Chest X-ray (antero-posterior projection) demonstrating a septic lesion (thick arrow)

Despite the significant improvements in both diagnostic and therapeutic procedures in recent years, infective endocarditis (IE) remains a medical challenge due to poor prognosis and high mortality. IE varies according to the initial clinical manifestations, underlying cardiac disease, micro-organisms involved and the associated complications. Echocardiographically, the majority of patients demonstrate vegetations on a single valve, while demonstration of involvement of two valves occurs much less frequently; triple-valve involvement is extremely rare. In a series of 25 opiate addicts with echocardiographic evidence of valvular vegetations, no cases of triple-valve involvement were found.1 In a recent case-series of 77 patients with IE, the incidence of multi-valvular endocarditis (MVE) was 18%, with mitral and aortic valves most commonly affected.2

Figure 2. Chest computed tomography (CT) (coronal plane) demonstrating septic embolus (thick arrow)
Figure 2. Chest computed tomography (CT) (coronal plane) demonstrating septic embolus (thick arrow)

We present a case of a young, ex-intravenous drug user with triple-valve IE, who was managed successfully medically with a brief review of the published literature.

Case report

A 48-year-old man presented with non-specific symptoms of lethargy, anorexia and significant weight loss. He was an ex-intravenous drug user. The examination revealed a cachectic appearing male with a temperature of 37°C, a blood pressure of 83/57 mmHg and a pulse of 100 beats per minute. There were no clinical signs of IE or fresh ‘needle-track’ signs to note. His chest was clear to auscultation and his abdomen was soft and non-tender to palpation. Cardiovascular examination revealed a loud pan-systolic murmur along with an early diastolic murmur. Laboratory investigations showed a mild, normocytic anaemia, normal white cell and neutrophil count, but an elevated C-reactive protein (CRP). His non-specific presentation and laboratory results, together with examination findings, raised the suspicion of IE as a diagnosis, and three sets of blood cultures were drawn. Empirical antibiotics were started as per guideline recommendations. Chest X-ray also showed a small, well-demarcated mid-zone lesion, which was thought to be a septic lesion (figure 1). In view of the lesion on the chest X-ray, a computed tomography (CT) scan of the thorax was done that demonstrated a septic embolus (figure 2).

Figure 3. Transoesophageal echocardiogram showing vegetation attached to the aortic valve (thick arrow)
Figure 3. Transoesophageal echocardiogram showing vegetation attached to the aortic valve (thick arrow)

Transthoracic echocardiography (TTE) revealed an echogenic mass on the aortic valve. Subsequent transoesophageal echocardiography (TOE) revealed moderate-to-severe aortic regurgitation and vegetations on the tricuspid, pulmonary and aortic valves (figures 3 and 4). The large prolapsing vegetation on the regurgitant aortic valve was also noted to be transiently in contact with the septal wall at the site where mural vegetation growth was seen (figure 5). There was also noted to be a patent foramen ovale with intermittent right-to-left shunting. All blood culture sets became positive for Streptococcus mutans after 48 hours and were shown to be fully sensitive to penicillin (minimum inhibitory concentration [MIC] 0.023 mg/L). His antibiotic regimen was, thus, altered to match sensitivities.

Streptococcus mutans is usually a left-sided organism. It can only be presumed that inoculation of the opposite side of the heart has occurred by means of the patent foramen ovale as he had intermittent right-to-left shunt, but the predominant shunt appeared to be from left to right.

Figure 4. Transoesophageal echocardiogram showing vegetations on tricuspid (thick, long arrow), aortic (thin arrow) and pulmonic valves (thick, short arrow)
Figure 4. Transoesophageal echocardiogram showing vegetations on tricuspid (thick, long arrow), aortic (thin arrow) and pulmonic valves (thick, short arrow)

His eventual antibiotic regimen was administered through a peripherally inserted central catheter (PICC) line and consisted of treatment with gentamicin for two weeks, together with benzylpenicillin for six weeks, followed by vancomycin for one week, with return of both his CRP and temperature to normal. No plans for imminent surgical intervention were made on the wishes of the patient, and he was discharged home. His weekly repeated blood tests showed no evidence of infection for six weeks. He remained well and asymptomatic when reviewed in the clinic after three months.

Discussion

The major bulk of echocardiographically proven endocarditis occurs on a single valve. The involvement of two valves is much less common, and triple – or quadruple – valve involvement has very rarely been reported. Kim et al.2 described that multi-valve endocarditis represents a separate clinical entity, recognised to be an independent risk factor affecting survival. It was demonstrated that the mortality rate was higher in patients with infection of two or more valves than in patients with involvement of a single valve (21% vs. 18%, respectively). Furthermore, patients with involvement of multiple valves had an increased rate of complications, such as congestive cardiac failure (64%) and acute renal failure (50%) that often required early surgery.2

Figure 5. Transoesophageal echocardiogram showing vegetations on the aortic valve (thin, long arrow) and the mural wall (thick, short arrow)
Figure 5. Transoesophageal echocardiogram showing vegetations on the aortic valve (thin, long arrow) and the mural wall (thick, short arrow)

López et al.3 reported that in MVE, independent predictors of hospital mortality were heart failure and persistent infection. It was demonstrated that persistent infection increased the risk of in-hospital mortality four-fold. Persistent infection reflects that failure of antibiotic treatment to control the infectious process.4 Because of the dire prognosis, patients in this clinical situation should be treated surgically. López et al.3 found no difference in the demographic or microbiologic profile between MVE and single-valve endocarditis (SVE). Although MVE was more frequently associated with the appearance of heart failure than SVE, short-term mortality was similar in both groups, probably because of the more aggressive therapeutic management of MVE.

The current European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) guidelines5,6 recommend that surgical treatment should be performed in native valve IE, when the following indications are present:

  • Development of heart failure, especially if moderate or severe
  • Severe aortic or mitral regurgitation with evidence of abnormal haemodynamic status
  • Endocarditis caused by fungi or other resistant organisms
  • Peri-valvular infection with fistula or abscess formation
  • Signs of uncontrolled infection such as persistent fever and positive blood cultures beyond 7 to 10 days of appropriate antibiotic therapy.

Other possible indications include:

  • Embolic events, in spite of adequate antibiotic therapy, or associated with vegetations >10 mm in diameter
  • Presence of vegetations >10 mm, with or without embolic events, if mobile and associated with other signs of severe illness.

The current guidelines5,6 recommend that surgical treatment should generally be avoided in patients with right-sided IE, although it has to be considered in the following situations:

  • Right-sided IE secondary to severe tricuspid regurgitation with a poor response to diuretic therapy
  • IE caused by organisms that are difficult to eradicate or bacteraemia for at least seven days, despite adequate antimicrobial therapy
  • Tricuspid valve vegetations >20 mm that persist after recurrent pulmonary emboli, with or without concomitant right heart failure.

MVE is a poorly studied entity, and there is little information regarding its main characteristics, prognosis, and the best management approach. Despite the advancements in operative techniques in the recent years, triple-valve surgery remains challenging. The few published studies include small numbers of patients, and did not reflect the characteristics of the general population with endocarditis.2,7 The results of these studies are contradictory: some associate multiple-valve disease with a worse prognosis,7 whereas others found no such association.2 Optimal therapeutic management also remains unclear; some studies suggest surgery improves the prognosis in patients with MVE,7 although concrete evidence is lacking. Further research and recommendations are needed in order to manage these complex patients in the best possible way.

Acknowledgement

The authors appreciate the support of the Department of Echocardiography, Royal Glamorgan Hospital, for their help in providing the images of the patient.

Conflict of interest

None declared.

Key messages

  • Multi-valve endocarditis (MVE) is a poorly studied entity with little information regarding its main characteristics, prognosis and management
  • MVE represents a separate clinical entity, recognised to be an independent risk factor affecting survival
  • Despite the recent advancements in operative techniques, multiple-valve surgery remains challenging
  • Further research is needed to explore and identify better management options in these patients.

References

1. Andy JJ, Sheikh MU, Ali N et al. Echocardiographic observations in opiate addicts with active infective endocarditis. Frequency of involvement of the various values and comparison of echocardiographic features of right- and left-sided cardiac valve endocarditis. Am J Cardiol 1977;40:17–23.

2. Kim N, Lazar JM, Cunha BA, Liao W, Minnaganti V. Multi-valvular endocarditis. Clin Microbiol Infect 2000;6:207–12. http://dx.doi.org/10.1046/j.1469-0691.2000.00065.x

3. López J, Revilla A, Vilacosta I et al. Multiple-valve infective endocarditis: clinical, microbiologic, echocardiographic, and prognostic profile. Medicine (Baltimore) 2011;90:231–6. http://dx.doi.org/10.1097/MD.0b013e318225dcb0

4. Revilla A, López J, Vilacosta I et al. Clinical and prognostic profile of patients with infective endocarditis who need urgent surgery. Eur Heart J 2007;28:65–71. http://dx.doi.org/10.1093/eurheartj/ehl315

5. Habib G, Lancellotti P, Antunes MJ et al. 2015 ESC Guidelines for the management of infective endocarditis. The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J 2015;36:3075–123. http://dx.doi.org/10.1093/eurheartj/ehv319

6. Nishimura RA, Otto CM, Bonow RO et al. 2014 AHA/ACC Guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129:e521–e643. http://dx.doi.org/10.1161/CIR.0000000000000031

7. Mihaljevic T, Byrne JG, Cohn LH, Aranki SF. Long-term results of multivalve surgery for infective multivalve endocarditis. Eur J ‎Cardiothorac Surg 2001;20:842–6. http://dx.doi.org/10.1016/S1010-7940(01)00865-X

Strain imaging and anthracycline cardiotoxicity

Br J Cardiol 2016;23:68–72doi:10.5837/bjc.2016.016 Leave a comment
Click any image to enlarge
Authors:

This was a pilot study, in which 55 breast cancer patients were enrolled, to evaluate the alterations of strain and strain-rate parameters in breast cancer patients receiving doxorubicin and compare them with serial conventional echocardiography changes. A week prior to, and a week after, chemotherapy with doxorubicin, left ventricular ejection fraction (LVEF) and strain and strain-rate parameters were measured by conventional 2D echocardiography and tissue Doppler-based imaging, respectively.

Comparison of the results of pre- and post-chemotherapy evaluation demonstrated that strain and strain-rate parameters were significantly reduced. Mean difference (standard deviation) for the strain measurement of basal-septal, basal-lateral, basal-inferior, and basal-anterior values were 2.58% (2.15), 3.20% (1.94), 4.13% (3.48), and 2.86% (2.65), respectively; and for the strain-rate values were 0.18 s–1 (0.17), 0.17 s–1 (0.17), 0.24 s–1 (0.19), and 0.19 s–1 (0.14), respectively; all p values <0.001. There was no significant change in patients’ LVEF after chemotherapy (pre-intervention 61.10 (4.86), post-intervention 61.06 (4.82), p=0.857). 

In conclusion, strain/strain-rate significant reduction, in the setting of normal range LVEF, suggests subclinical heart failure. Whether the strain and strain-rate imaging should replace the conventional echocardiography for early monitoring of cardiotoxicity of doxorubicin requires further investigations.

Introduction

Screen shot 2016-04-19 at 11.19.39Breast cancer is one of the major public health problems; it is the second most common cancer among women and it has a high mortality rate.1

Doxorubicin, which is an antibiotic of the anthracycline group, has a cytotoxic antineoplastic activity and is commonly used in a broad spectrum of malignancies, either alone or in combination with other drugs. Despite its usefulness in chemotherapy of breast cancer, its cardiac side effects, such as cardiomyopathy and congestive heart failure, cause considerable limitations and obstacles for oncologists and cardiologists.2,3

Doxorubicin’s cardiotoxicity is mainly due to oxidative stress, which is induced by the production of reactive oxygen species (ROS) and mitochondrial damage. Other suggested mechanisms include decreased number of contractile cells as a result of damage to mitochondrial and cellular membranes, and extracellular matrix remodelling.4,5

Although it is suggested that anthracycline-related cardiotoxicity is mainly related to cumulative dose of the drug, and the risk of cardiomyopathy increases with a higher cumulative anthracycline dose,6 subclinical cardiac changes have even been reported in patients treated with low-dose anthracycline.7,8 Also, it has been suggested that anthracycline infusion duration of six hours or longer reduces the risk of clinical heart failure, and seems to reduce the risk of subclinical cardiac damage, as well.6

Early detection of cardiac damage in still-reversible stage is fundamental because doxorubicin cardiotoxicity will eventually progress into irreversible phase, and detection of subclinical myocardial contractility impairment at a latent stage will allow early treatment and complete recovery.9

Declined left ventricular ejection fraction (LVEF) and shortening fraction at rest, which are found by assessing serial conventional echocardiographs, are the commonly used monitoring parameters for detection of chemotherapy-induced cardiomyopathy. The main drawback of these parameters is that the significant decline is detected when the cardiac dysfunction has become irreversible. In fact, they are not sensitive to early cardiac function alterations.4,10,11 Also, it has been demonstrated that a decline in systolic function may occur while the LVEF is still remaining within the normal range.10,12 Therefore, new echocardiographic methods such as tissue Doppler imaging (TDI) and two-dimensional (2D)-speckle tracking (STE), magnetic resonance imaging (MRI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and troponin I (TnI) are suggested for early detection of cardiac dysfunction.12-17

Recent studies suggest that strain and strain-rate imaging provide more sensitive and reproducible measurement of anthracycline-induced myocardial systolic changes rather than standard echocardiographic parameters, especially early after therapeutic doses of anthracycline chemotherapy when LVEF is still within normal limits.18-23 However, strain and strain-rate parameters have some limitations for patients suffering from obesity, valvular cardiac diseases, myocardial infarction, left ventricle hypertrophy and infiltrative diseases.10

The aim of the present study is to assess the alterations of strain and strain-rate imaging findings and compare them with conventional echocardiographic parameters in breast cancer patients receiving doxorubicin as part of their chemotherapy; and evaluate their efficacy in early identification of anthracycline-induced cardiotoxicity.

Materials and methods

Study settings and approval

This pilot study was conducted at University Hospitals and approved by the Ethics Committee of Mashhad University of Medical Sciences (No. 89233). It is also submitted in Iran Registry of Clinical Trials with the registry number IRCT2014060112924N2. Written informed consent was obtained from all patients.

Subjects

Fifty-five female patients with pathologically confirmed non-metastatic breast cancer detected between 2010 and 2013 were enrolled in this study. The inclusion criteria were as follows: menstruating women with no cardiac risk factors such as previous cardiac diseases (including ischaemic heart disease, prolonged hypertension, congenital or acquired valvular diseases and any kind of myocardial diseases) and diabetes, no previous chemo/radiotherapy or any kind of cancers, and no contraindication to doxorubicin (hypersensitivity to the drug, pregnancy, lactation, radiotherapy, congestive heart failure, cardiomyopathy, or myelo-suppression). The exclusion criteria were as follows: new-onset cardiac symptoms or atrial fibrillation, unsatisfactory echocardiography and lack of patient’s compliance with the drug or echocardiography.

Anthropometric parameters

For all participants, anthropometric parameters including weight and height, as well as vital signs including heart rate, blood pressure, temperature and respiratory rate were measured, using a standard protocol. Height and body weight were measured with the subjects dressed in light clothing after an overnight fast. The body mass index (BMI) was calculated as weight (kg) divided by height squared (m2). Body surface area was calculated using DuBois and DuBois equation (weight [kg]0.425 × height [cm]0.725 × 0.007184). Patients with a BMI over 30 kg/m2 were considered as obese.

Chemotherapy

Chemotherapy, based on NCCN (National Comprehensive Cancer Network) guideline, was performed using doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) cycled every 21 days for four cycles (cumulative dose of doxorubicin was 240 mg/m2) followed by paclitaxel (175 mg/m2) cycled every 21 days for four cycles. Doxorubicin contraindications were evaluated for all patients prior to commencing the therapy.

Cardiac monitoring and echocardiography

A cardiologist visited each patient every month during the intervention and the exclusion criteria were evaluated. Echocardiography was performed one week before commencing the chemotherapy and one week after the fourth cycle of doxorubicin. Strain and strain-rate parameters, as well as LVEF, were evaluated. In all patients, the agent was discontinued in case of a 10% drop in ejection fraction or a drop to less than 30%.

Conventional 2D echocardiography was performed using commercially available equipment (Vivid-7, General Electric Vingmed, Horten, Norway). Patients were imaged in the left lateral decubitus position and data were acquired with a 3.5 MHz transducer in the parasternal (long- and short-axis views) and apical views (two- and four-chamber and apical long-axis views).

Comprehensive assessment of left ventricular myocardial strain and strain rate was performed using TDI-based imaging by a cardiologist who was blinded to the patients’ information. For this purpose, standard 2D grey-scale images of the left ventricle were acquired at conventional apical two- and four-chamber views, with a mean frame rate of 90 ± 5 frames per second (fps). Basal values are considered to represent the best reproducibility for TDI-based strain assessment, therefore, only this view was evaluated. Data were stored in cine-loop format and analysed by two persons (blinded to patients’ information).

Peak systolic longitudinal strain and strain rate was calculated and derived from the four segments of the two apical views (two- and four-chamber views). Inter-observer variability was not evaluated because one person obtained all images.

Statistical analysis

All data analysis was performed using Statistical Package for the Social Sciences, 21st release (SPSS Science, Apache Software Foundation, and Chicago, IL, USA). Absolute numbers and percentages were computed to describe data. Also, data were expressed as mean ± standard deviation (SD) for continuous variables. Paired-sample t-test was utilised to compare the alterations of normally distributed parameters before and after the intervention. Also, related-samples Wilcoxon signed-rank test was utilised for non-parametric parameters. A two-sided p value <0.05 was considered significant.

Results

Fifty-five women diagnosed with breast cancer were enrolled in this study from which three patients were excluded due to their refusal to continue participation in the study. Echocardiography was performed for all patients prior to the intervention and after completion of chemotherapy. During regular cardiologist visits, none of the patients presented any kind of cardiac symptoms.

Demographic and baseline characteristics

Patients’ demographic data are summarised in table 1. Neither obese nor hypertensive patients were included, hence, any new-onset cardiac symptom or alteration in echocardiographic values can be roughly considered as due to chemotherapy cardiotoxicity.

Table 1. Patients’ demographic data
Table 1. Patients’ demographic data

Echocardiography findings

There was no abnormality in patients’ diastolic function prior the intervention. A moderate mitral regurgitation (1.9%) and four moderate tricuspid regurgitations (7.7%) were found among the patients from whom none had a history of cardiopulmonary symptoms. Other valvular evaluations were normal. Pulmonary artery pressure was within the normal range in all patients. Echocardiographic baseline characteristics are summarised in table 2.

Table 2. Echocardiographic baseline values
Table 2. Echocardiographic baseline values

Comparison of the echocardiographic findings prior to and after intervention clarified that strain and strain-rate parameters were significantly decreased in all four evaluated walls, while there was no considerable change in LVEF. There was no alteration among other parameters after the intervention. For ease of interpretation, the data are presented in table 3.

Table 3. Comparison of the echocardiographic parameters pre- and post-intervention
Table 3. Comparison of the echocardiographic parameters pre- and post-intervention

Discussion

Early detection of cardiac dysfunction in patients receiving doxorubicin chemotherapy has become an important notable topic for oncologists and cardiologists. Especially because of the fact that it would provide patients with better management and the chance of increased survival with lower additional side effects.

In the present study, data analysis showed that in breast cancer patients receiving 240 mg/m2 of doxorubicin as part of the chemotherapy, strain and strain-rate parameters were significantly reduced after treatment, while there was no significant change in LVEF. These findings suggest that strain and strain-rate parameters evaluated by TDI could be considered as the routine monitoring method in breast cancer patients receiving doxorubicin.

LVEF

There is controversy among the studies published on assessment and monitoring of anthracycline-induced cardiotoxicity, in terms of using LVEF changes as a definition. Also, there is limited evidence-based consensus due to different chemotherapy regimens, assessment methods, and cut-offs used in different studies.11

This study revealed no significant change in LVEF in breast cancer patients treated with doxorubicin, which is supported by a report by Jurcut et al.20 In contrast with our results, Chung et al. found this alteration significant.24 Their retrospective study showed a considerable decrease in LVEF, especially in patients receiving more than 300 mg/m2 of doxorubicin, which was the case in 39 out of 174 evaluated patients. Since all of our patients received 240 mg/m2 of the drug during chemotherapy, this could be a possible explanation for the more dramatic results observed by Chung et al. Moreover, while patients who were enrolled in the Chung et al. study had different kinds of cardiac risk factors, patients who were enrolled in the present study had no cardiac risk factors. Results considering the LVEF alterations during anthracycline chemotherapy are controversial. Although some studies suggest that monitoring serial LVEF is a reliable measurement for identifying cardiac dysfunction, others believe that this index is not sensitive enough.25

Strain and strain rate

Strain and strain-rate parameters demonstrated a significant decrease in all four evaluated walls in this study. Jurcut et al. found the same results on evaluation of 16 breast cancer patients treated with doxorubicin.20 In contrast, Stoodley et al. reported a significant decrease in strain parameters without any considerable change in strain-rate parameters.12 They set the frame rate of echocardiography between 50 to 70 fps, but our design was to perform the strain and strain-rate imaging within the range of 90 ± 5 fps. Hence, using a more precise and sensitive method for strain-rate assessment lead to detection of even small amounts of reduction in these indices in our study.

Limitations

This study was unable to evaluate the radial and circumferential strain and strain rate, as well as global, due to limited available software. Also inherent limitations in Doppler-based imaging preclude an accurate assessment. To prevent this, the echocardiography operator in this study tried to get the best image orientation and sample volume position, and as high a frame rate as possible.

Since, following doxorubicin, patients were treated with paclitaxel and radiotherapy, both of which are known to be cardiotoxic, long-term follow-up was not feasible without lots of confounding factors.

Conclusion

Data analysis demonstrated that strain and strain-rate parameters had significant reduction in patients who received doxorubicin as the chemotherapy, while there was no considerable change in LVEF. It seems that strain and strain-rate imaging provide a more sensitive and reliable measurement for early detection of cardiac dysfunction in patients who are under chemotherapy with an anthracycline.

This would not only help in better management of cancer treatment by early detection of cardiac dysfunction, but also would improve the outcome by providing supportive additional therapies in patients who receive cardiotoxic regimens.

Acknowledgements

The source of funding for this study was Mashhad University of Medical Sciences. We sincerely thank all the employees of the chemotherapy ward of Qaem Hospital for their cooperation. Also we thank Dr Babaei for his help in patient enrolment.

Conflict of interest

None declared.

Key messages

  • Cancer patients undergoing chemotherapy can develop silent cardiac dysfunction, which can remain undetected by routine echocardiography
  • Strain and strain-rate imaging provide a more sensitive and reliable measurement for early detection of cardiac dysfunction in these patients
  • These parameters could be considered as the routine monitoring method in breast cancer patients receiving doxorubicin

References

1. Ban KA, Godellas CV. Epidemiology of breast cancer. Surg Oncol Clin N Am 2014;23:409–22. http://dx.doi.org/10.1016/j.soc.2014.03.011

2. Tashakori Beheshti A, Mostafavi Toroghi H, Hosseini G, Zarifian A, Homaee Shandiz F, Fazlinejad A. Carvedilol administration can prevent doxorubicin-induced cardio-toxicity: a double-blinded randomized trial. Cardiology 2016;134:47–53. http://dx.doi.org/10.1159/000442722

3. Nelson-Veniard M, Thambo JB. [Chemotherapy-induced cardiotoxicity: incidence, diagnosis and prevention]. Bull Cancer 2015;102:622–6. http://dx.doi.org/10.1016/j.bulcan.2015.03.014

4. Monte I, Bottari VE, Buccheri S et al. Chemotherapy-induced cardiotoxicity: subclinical cardiac dysfunction evidence using speckle tracking echocardiography. J Cardiovasc Echography 2013;23:33–8. http://dx.doi.org/10.4103/2211-4122.117983

5. Nikitovic D, Juranek I, Wilks MF et al. Anthracycline-dependent cardiotoxicity and extracellular matrix remodeling. Chest 2014;146:1123–30. http://dx.doi.org/10.1378/chest.14-0460

6. Von Hoff DD, Layard MW, Basa P et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 1979;91:710–17. http://dx.doi.org/10.7326/0003-4819-91-5-710

7. Drafts BC, Twomley KM, D’Agostino R Jr. et al. Low to moderate dose anthracycline-based chemotherapy is associated with early noninvasive imaging evidence of subclinical cardiovascular disease. JACC Cardiovasc Imaging 2013;6:877–85. http://dx.doi.org/10.1016/j.jcmg.2012.11.017

8. van Dalen EC, van der Pal HJ, Caron HN et al. Different dosage schedules for reducing cardiotoxicity in cancer patients receiving anthracycline chemotherapy. Cochrane Database Syst Rev 2009;(4):Cd005008. http://dx.doi.org/10.1002/14651858.cd005008.pub3

9. Cardinale D, Colombo A, Lamantia G et al. Anthracycline-induced cardiomyopathy clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol 2010;55:213–20. http://dx.doi.org/10.1016/j.jacc.2009.03.095

10. Jiji RS, Kramer CM, Salerno M. Non-invasive imaging and monitoring cardiotoxicity of cancer therapeutic drugs. J Nucl Cardiol 2012;19:377–88. http://dx.doi.org/10.1007/s12350-012-9512-2

11. Plana JC, Galderisi M, Barac A et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 2014;15:1063–93. http://dx.doi.org/10.1093/ehjci/jeu192

12. Stoodley PW, Richards DA, Hui R et al. Two-dimensional myocardial strain imaging detects changes in left ventricular systolic function immediately after anthracycline chemotherapy. Eur J Echocardiogr 2011;12:945–52. http://dx.doi.org/10.1093/ejechocard/jer187

13. Cottin Y, Touzery C, Coudert B et al. Impairment of diastolic function during short-term anthracycline chemotherapy. Br Heart J 1995;73:61–4. http://dx.doi.org/10.1136/hrt.73.1.61

14. Dodos F, Halbsguth T, Erdmann E et al. Usefulness of myocardial performance index and biochemical markers for early detection of anthracycline-induced cardiotoxicity in adults. Clin Res Cardiol 2008;97:318–26. http://dx.doi.org/10.1007/s00392-007-0633-6

15. Wassmuth R, Lentzsch S, Erdbruegger U et al. Subclinical cardiotoxic effects of anthracyclines as assessed by magnetic resonance imaging – a pilot study. Am Heart J 2001;141:1007–13. http://dx.doi.org/10.1067/mhj.2001.115436

16. Sawaya H, Plana JC, Scherrer-Crosbie M. Newest echocardiographic techniques for the detection of cardiotoxicity and heart failure during chemotherapy. Heart Fail Clin 2011;7:313–21. http://dx.doi.org/10.1016/j.hfc.2011.03.003

17. Christenson ES, James T, Agrawal V et al. Use of biomarkers for the assessment of chemotherapy-induced cardiac toxicity. Clin Biochem 2015;48:223–35. http://dx.doi.org/10.1016/j.clinbiochem.2014.10.013

18. Poterucha JT, Kutty S, Lindquist RK et al. Changes in left ventricular longitudinal strain with anthracycline chemotherapy in adolescents precede subsequent decreased left ventricular ejection fraction. J Am Soc Echocardiogr 2012;25:733–40. http://dx.doi.org/10.1016/j.echo.2012.04.007

19. Fedele C, Riccio G, Coppola C et al. Comparison of preclinical cardiotoxic effects of different ErbB2 inhibitors. Breast Cancer Res Treat 2012;133:511–21. http://dx.doi.org/10.1007/s10549-011-1783-9

20. Jurcut R, Wildiers H, Ganame J et al. Strain rate imaging detects early cardiac effects of pegylated liposomal doxorubicin as adjuvant therapy in elderly patients with breast cancer. J Am Soc Echocardiogr 2008;21:1283–9. http://dx.doi.org/10.1016/j.echo.2008.10.005

21. Khouri MG, Hornsby WE, Risum N et al. Utility of 3-dimensional echocardiography, global longitudinal strain, and exercise stress echocardiography to detect cardiac dysfunction in breast cancer patients treated with doxorubicin-containing adjuvant therapy. Breast Cancer Res Treat 2014;143:531–9. http://dx.doi.org/10.1007/s10549-013-2818-1

22. Luis SA, Yamada A, Khandheria BK et al. Use of three-dimensional speckle-tracking echocardiography for quantitative assessment of global left ventricular function: a comparative study to three-dimensional echocardiography. J Am Soc Echocardiogr 2014;27:285–91. http://dx.doi.org/10.1016/j.echo.2013.11.002

23. Miyoshi T, Tanaka H, Kaneko A et al. Left ventricular endocardial dysfunction in patients with preserved ejection fraction after receiving anthracycline. Echocardiography 2014;31:848–57. http://dx.doi.org/10.1111/echo.12473

24. Chung WB, Yi JE, Jin JY et al. Early cardiac function monitoring for detection of subclinical doxorubicin cardiotoxicity in young adult patients with breast cancer. J Breast Cancer 2013;16:178–83. http://dx.doi.org/10.4048/jbc.2013.16.2.178

25. Mele D, Rizzo P, Pollina AV et al. Cancer therapy-induced cardiotoxicity: role of ultrasound deformation imaging as an aid to early diagnosis. Ultrasound Med Biol 2015;41:627–43. http://dx.doi.org/10.1016/j.ultrasmedbio.2014.11.015

When you can’t obtain a history…

Br J Cardiol 2016;23:78doi:10.5837/bjc.2016.017 Leave a comment
Click any image to enlarge
Authors:

A 79-year-old lady was taken to the emergency department by her carer, who had noticed an acute deterioration of her general condition. Unfortunately, it was difficult to obtain an accurate history from the patient due to cognitive impairment, and her carer was not aware of her past medical history. However, she had been observed clenching her hands to her chest. She was not previously known to the admitting hospital.

Figure 1. Patient chest X-ray showing a ‘full metal jacket’
Figure 1. Patient chest X-ray showing a ‘full metal jacket’

Her physical examination and vital signs were unremarkable. Routine blood tests had been requested. Resting 12-lead electrocardiogram (ECG) showed left bundle branch block; no previous ECGs were available for comparison. A chest X-ray was performed, which gave another clue to the diagnosis…

The chest radiograph (figure 1) shows clear lung fields, normal cardiac contour and, more importantly, a radio-opaque structure across the anterior surface of her heart. This is sometimes termed a ‘full metal jacket’, implying extensive stenting of a coronary artery in its entirety from percutaneous coronary intervention (PCI); in this case, across her left anterior descending artery. This was later confirmed by the patient’s daughter, who reported her mother had undergone multiple PCI procedures in the past. Therefore, acute coronary syndrome (ACS) was suspected, and subsequently confirmed by raised cardiac biomarkers. The patient was successfully treated with medical therapy for ACS and discharged three days later: she was not offered repeat coronary angiography on this occasion due to her clinical presentation and cognitive impairment.

While the classical triad for the diagnosis of ACS is given by a combination of chest pain, ECG changes and elevation of cardiac biomarkers, other basic investigations may play a significant role in formulating the correct diagnosis, particularly in complex circumstances, as in the case we present with this report.

Conflict of interest

None declared.

Update from the 8th BSH Day for Revalidation and Training

Br J Cardiol 2016;23:(1) Leave a comment
Click any image to enlarge

A wide array of investigations is available to the heart failure specialist. Their proper utilisation requires knowledge of their indications, and proficiency in interpretation. This was the focus of the second morning session, entitled “Different tests”, of the 8th British Society for Heart Failure (BSH) Training and Revalidation Day. Held on 3rd March 2016, at the Golden Jubilee National Hospital, Clydebank, this session included excellent presentations on cardiopulmonary exercise testing (CPET), cardiac catheterisation in heart failure, assessment of haemodynamics using echocardiography, and the use of cardiac CT in heart failure. Dr Simon Beggs reports on some of the highlights from a lively and thought-provoking day.

CPET: an overview of “the cardiac cycle”

Screen shot 2016-01-28 at 11.56.38The breathless patient with heart failure and comorbidity can pose a diagnostic conundrum: is the dyspnoea cardiac or respiratory (or something else entirely)? Dr Christopher Boos (Poole Hospital NHS Foundation Trust) outlined the role of cardiopulmonary exercise testing (CPET) in such situations.

CPET integrates a broad range of variables related to cardiorespiratory function, including oxygen uptake and expiratory ventilation, along with blood pressure and electrocardiogram (ECG) tracing. It provides objective information on physiological performance under stress: key output data include peak VO2 (a measure of maximal aerobic capacity), anaerobic threshold (AT), respiratory exchange ratio (RER) and breathing reserve (BR).

Determination of the primary aetiology in unresolved cases of dyspnoea is aided by proper interpretation of these data. Dr Boos illustrated this with two case examples.

First, he presented a 54-year old male with a left ventricular ejection fraction (LVEF) of 25%, BMI of 33 and exertional dyspnoea, in whom a relatively normal AT, moderately impaired VO2 and normal BR indicated deconditioning as the primary cause of his presentation. Second, a 49-year old female with severe interstitial lung disease and moderate-to-severe mitral stenosis, in whom a low AT and high BR suggested valve disease as the principal aetiology of her dyspnoea. In both cases, CPET facilitated a confident diagnosis and altered patient management.

Wither the cardiac catheter?

Invasive assessment of the coronary anatomy and cardiac haemodynamics are oft- used tools in the cardiologist’s armoury. The précis of Professor Andrew Clark’s (University of Hull) talk was that the former adds little value in the assessment of patients with heart failure, whilst the latter’s worth is underappreciated.

The STICH1 and HEART2 trials failed to show significant mortality benefit from coronary revascularisation in patients with heart failure. The benefit of routine coronary angiography in these patients is dubious.

Meanwhile, right heart catheterisation (RHC) may provide valuable diagnostic and prognostic data. Both procedural technique and knowledge of typical haemodynamic waveforms are vital. In cardiac transplant candidates, assessment of right heart data including pulmonary artery pressure, transpulmonary gradient and pulmonary vascular resistance is essential: unacceptable parameters contraindicate transplantation. RHC also provides a route by which to perform endomyocardial biopsy when indicated, such as in suspected infiltrative cardiac disorders.

Simultaneous left and right heart catheterisation may help discern the aetiology of heart failure. For example, the classic “dip and plateau” sign resulting from diastolic equalisation of cardiac pressures in constrictive pericarditis (see figure 1). Similarly, RHC occasionally detects unsuspected congenital anomalies, such as atrial septal defects (ASDs), via inappropriate “step-up” in venous oxygen saturations.

Figure 1. Simultaneous right- and left-heart catheterisation demonstrating the “dip and plateau” pattern a patient with constrictive pericarditis
Figure 1. Simultaneous right- and left-heart catheterisation demonstrating the “dip and plateau” pattern in a patient with constrictive pericarditis

Professor Clark concluded that assessment of cardiac haemodynamics is a vital competency for the heart failure specialist, and one requiring both technical and analytical rigour. A recent review of the subject is available.3

Assessment of haemodynamics with echocardiography

Assessment of cardiac haemodynamics is also feasible non-invasively. Dr Alison Duncan (Royal Brompton Hospital, London) summarised advantages and pitfalls of echocardiography used for this purpose.

Echocardiographic estimation of intra-cardiac pressure gradients and valve areas using the Bernoulli and Continuity Equations is common practice. Mean aortic valve gradient by echocardiography correlates with catheter-based measurements, although operators must recall that measurements by these modalities are not equivalent. Cross-sectional area calculations can be extended to non-valvular orifices, such as ASDs.

Other echo-derived haemodynamic parameters are clinically relevant: cardiac output and systemic vascular resistance, for example. Left atrial pressure (LAP) may be estimated via velocity quantification of the mitral regurgitant jet.

Dr Duncan further demonstrated how left ventricular filling patterns are readily understood from physiology. The intraventricular relaxation time (IVRT) lengthens with impaired LV relaxation. Eventually this curtails the mitral inflow E wave (passive filling), necessitating a compensatory dominant A wave (active filling), thus producing the classic reversed E:A ratio of LV diastolic dysfunction. Conversely, prolonged restrictive physiology and a high LAP results in a dominant, “spiky” E wave, producing a “pseudonormal” pattern.

The clinician must be aware that LV loading can alter echocardiographic filling patterns in such situations. For example, markedly different results may be obtained in the same patients before and after renal dialysis. This, as Dr Duncan pointed out, is a reminder that clinical assessment of the patient remains essential when utilising echocardiography.

Cardiac CT: what role in heart failure?

The emergence of 64-slice multi-detector computed tomography (MDCT) over the last decade has delivered high spatial and temporal resolution; an entire heart can be imaged in less than 15 seconds. In a visually spectacular epic, Dr Ronak Rajani (Guy’s and St Thomas’ Hospitals, London) predicted an increasing role for MDCT in the management of patients with heart failure.

Ischaemic cardiomyopathy remains a leading cause of heart failure. MDCT has a growing role in the definition of anatomic coronary stenosis, detection of high-risk coronary plaque features, and non-invasive functional assessment of coronary disease via FFRct, enabled by the application of computational fluid dynamics.

There is advocacy of MDCT for evaluation of aetiology and severity of left ventricular dysfunction,4,5 and a recent meta-analysis concluded that, along with 3D echocardiography, MDCT had the narrowest limits of agreement in assessment of LVEF when compared to cardiac MRI.6 Looking forward, new Spectral and Dual Energy CT technologies promise to revolutionise myocardial characterisation.

Dr Rajani proposed that MDCT may soon provide a “one stop shop” for cardiac resynchronisation therapy patients, via assessment of scar burden, ventricular function, mechanical dyssynchrony via endocardial strain and deformation, and anatomical mapping of the coronary venous system. In patients with left ventricular assist device (LVADs), MDCT can already provide assessment of device alignment and presence of thrombus. The application of computational fluid dynamics might in the future enable sophisticated MDCT-based analyses of LVAD function. Dr Rajani’s message was clear: the capabilities of MDCT are widening and deepening, and its application to patients with heart failure looks set to grow.

Dr Simon Beggs

Clinical fellow, Scottish National Advanced Heart Failure Service

Golden Jubilee National Hospital, Agamemnon St, Clydebank, Dunbartonshire G81 4DY

Acknowledgements

The BSH gratefully acknowledges the support provided by the Friends of BSH:

Bayer HealthCare, Biotronik, Boston Scientific, Medtronic, Novartis, Roche Diagnostics, Servier Laboratories, St. Jude Medical and Vifor Pharma.

Diary Dates

19th BSH Annual Autumn Meeting, 24–25 November 2016, QE II Centre, London

9th BSH Heart Failure Day for Revalidation and Training, 2 March 2017, London

7th BSH Heart Failure Nurse Study Day, 3 March 2017, London

Contact

British Society for Heart Failure

E-mail: [email protected]

www.bsh.org.uk

References

1. Velazquez EJ, Lee KL, Deja MA, et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med 2011;364:1607–1. http://dx.doi.org/10.1056/NEJMoa1100356

2. Cleland JG, Calvert M, Freemantle N, et al. The Heart Failure Revascularisation Trial (HEART). Eur J Heart Fail 2011;13:227–33. http://dx.doi.org/10.1093/eurjhf/hfq230

3. Callan P, Clark AL. Right heart catheterisation: indications and interpretation. Heart 2016;102:147–57. http://dx.doi.org/10.1136/heartjnl-2015-307786

4. Tummala LS, Young RK, Singh T, et al. Role of non-invasive imaging in the work-up of cardiomyopathies. Curr Atheroscler Rep 2015;17:486. http://dx.doi.org/10.1007/s11883-014-0486-1

5. Taylor AJ, Cerqueira M, Hodgson JM, et al. ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 Appropriate use criteria for cardiac computed tomography. Circulation 2010;122:e525–e555. http://dx.doi.org/10.1161/CIR.0b013e3181fcae66

6. Pickett CA, Cheezum MK, Kassop D, et al. Accuracy of cardiac CT, radionucleotide and invasive ventriculography, two- and three-dimensional echocardiography, and SPECT for left and right ventricular ejection fraction compared with cardiac MRI: a meta-analysis. Eur Heart J Cardiovasc Imaging 2015;16:848–52. http://dx.doi.org/10.1093/ehjci/jeu313

NICE quality standard on acute heart failure

Br J Cardiol 2016;23:9 Leave a comment
Click any image to enlarge
Authors:

The National Institute for Health and Care Excellence (NICE) has published a new quality standard in acute heart failure (QS103) to cover the care of adults (over 18 years) who have a diagnosis of acute heart failure or are being investigated for acute heart failure. 

Acute heart failure is a common cause of admission to hospital with over 67,000 admissions in England and Wales a year, and is the leading cause of hospital admission in people 65 years or older in the UK. NICE expects the six quality statements will help improve outcomes from this condition.

The six quality statements are:

  • Adults presenting to hospital with new suspected acute heart failure have a single measurement of natriuretic peptide.
  • Adults admitted to hospital with new suspected acute heart failure and raised natriuretic peptide levels have a transthoracic doppler 2D echocardiogram within 48 hours of admission.
  • Adults admitted to hospital with acute heart failure have input within 24 hours of admission from a dedicated specialist heart failure team.
  • Adults with acute heart failure due to left ventricular systolic dysfunction are started on, or continue with, beta‑blocker treatment during their hospital admission.
  • Adults admitted to hospital with acute heart failure and reduced left ventricular ejection fraction are offered an angiotensin‑converting enzyme (ACE) inhibitor and an aldosterone antagonist.
  • Adults with acute heart failure have a follow‑up clinical assessment by a member of the community – or hospital‑based specialist heart failure team within two weeks of hospital discharge.

The full guidance is available at https://www.nice.org.uk/guidance/qs103

The long-term management of chronic heart failure is not covered by this quality standard but is covered in separate guidance: NICE guideline (CG108) and quality standard referral (QS9).

Obesity quality standard

NICE has also recently published a quality standard (QS111) ‘Obesity in adults: prevention and lifestyle weight management programmes’. One of the standards advises general practice teams and other healthcare professionals to offer referral to a lifestyle weight management programme to any adult identified as overweight or obese with comorbidities.

For more information on the new obesity quality standards, the full guidance is available at https://www.nice.org.uk/guidance/qs111

Confusing NICE guidance on PCSK9 inhibitors

Br J Cardiol 2016;23:9 Leave a comment
Click any image to enlarge
Authors:

The cholesterol charity, HEART UK, has questioned NICE’s decisions on the new PCSK9 inhibitors evolocumab (Repatha®, Amgen) and alirocumab (Pralulent®, Sanofi Regeneron), which were approved in Europe in May 2015 and in the USA in August 2015 for patients who are unable to control their cholesterol with current therapies. 

Jules Payne hopes NICE will 'see sense' about the PCSK9 inhibitors
Jules Payne hopes NICE will ‘see sense’ about the PCSK9 inhibitors

In November 2015, NICE published draft guidance not recommending evolocumab as an option for people with high cholesterol (primary hypercholesterolaemia – heterozygous familial and non-familial) and mixed dylipidaemia. A similar decision for alirocumab followed in February 2016, although only a few days before, the earlier decision for evolocumab had been modified by NICE who said that it could be used for a limited number of NHS patients who are considered to be statin intolerant.

HEART UK Chief Executive Ms Jules Payne said: “NICE appear to be confused about the effectiveness of this life-saving medication. It says ‘yes’ to one medicine one week and the next it says ‘no’ to another, and both are exactly the same.

“HEART UK was at the NICE meeting when it discussed these medicines and there were no lipidologists present who could give expert advice, so it’s hardly surprising the decision is so confused.”

“This flip-flopping approach to decision-making by NICE and not drawing on clinicians who are experts in this condition, undermines public confidence and denies patients access to potentially life-saving medication”.

She hopes NICE will “see sense” as it has in the case of the cholesterol-lowering drug ezetimibe. “HEART UK is delighted that NICE has listened to the concerns raised on behalf of healthcare professionals and patients to limit access to this life-saving medication”.

She hopes continued pressure from healthcare professionals will have a similar effect for the PCSK9 inhibitors. “HEART UK believes that denying access to PCSK9 inhibitors would leave a significant portion of patients at high risk without sufficient treatment options, which will put more pressure on the already-stretched NHS when the solution could save lives”.