The latest evidence in heart failure was presented at the 3rd Annual British Society of Heart Failure (BSH) medical training meeting, which took place in London, recently. Combining informative lectures from prominent figures in the field, together with interactive case presentations, the meeting was a resounding success, writes Dr Vikram Khanna.
The meeting set off to a stimulating start with Professor Theresa McDonagh (Kings College Hospital, Chair of the British Society of Heart Failure) reviewing primarily the growing evidence for aldosterone antagonists in the management of systolic heart failure (HF). Large clinical trials have established the role of aldosterone antagonists, such as spironolactone, in severe systolic HF (Randomised Aldactone Evaluation Study – RALES) and eplerenone in acute myocardial infarction (MI) complicated by left ventricular dysfunction (Eplerenone Post-Acute Myocardial Infarction Heart failure Efficacy and Survival Study – EPHESUS).
More recently the results of the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalisations and Survival Study in Heart Failure) study showed a reduction in cardiovascular death or admissions with HF when eplerenone was added to standard medical therapy in patients with mild symptoms (New York Heart Association class II functional status). As expected, there was a higher incidence of hyperkalaemia in patients treated with eplerenone, highlighting the importance of close monitoring of renal function in these patients.
Implantable cardiac defibrillator (ICD)
A session looking at the evidence for primary prevention device therapy started with a review of the original landmark studies by Dr Derek Connelly (Consultant Cardiologist, Glasgow Royal Infirmary). The MADIT-II (Multicentre Automatic Defibrillator Implantation Trial II) trial was the first major study to show a survival benefit for prophylactic ICD implantation in patients with previous MI and a left ventricular ejection fraction (LVEF) of less than 30%.
Most of the primary prevention ICD trials have focused on patients with ischaemic aetiology of HF. Dr Jay Wright (Consultant Cardiologist, Liverpool Heart and Chest Hospital) discussed the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) study, which also enrolled patients with non-ischaemic cardiomyopathy (NICM). This showed a similar relative risk reduction of death of 27% in the NICM group as compared to 21% in the ischaemic group. Nevertheless, the absolute risk reduction over five years was only a modest 7.2%, and this was cited as a possible reason as to why the National Institute for Health and Clinical Excellence (NICE) have not issued specific guidance on implantation of an ICD in the non-ischaemic population.
Cardiac resynchronisation therapy (CRT)
The CARE-HF (Cardiac Resynchronisation – Heart Failure) study was pivotal being the first to show that a CRT device without a defibrillator could reduce the risk of death from any cause by 36%, when compared to standard medical therapy. In his review of this study, Dr Connolly said that, crucially, a number of important patient groups were excluded from this seminal trial, such as those with permanent atrial fibrillation (AF), mild HF symptoms (New York Heart Association [NYHA] functional class I and II), or a narrow QRS duration (< 120 msec). Dr Paul Foley (Consultant Cardiologist, Wiltshire Cardiac Centre) was charged with the challenging task of reviewing the latest evidence for implanting CRT in these selective populations.
When considering AF, a large Italian cohort study has reported improvements in LVEF, NYHA class and exercise capacity, similar to those seen in sinus rhythm, when CRT is combined with AV node ablation. Nevertheless, there is consensus that there is insufficient evidence to support a mortality benefit with this strategy, and more prospective randomised studies are necessary.
The most compelling evidence for use of CRT in patients with mild HF symptoms comes from the MADIT-CRT (Multicentre Automatic Defibrillator Implantation Trial with Cardiac Resynchronisation Therapy) study, which enrolled patients in NYHA class I and II and randomised to ICD or CRT-D. This showed a 41% reduction in the risk of HF-events in the CRT-D group, which was primarily evident in a prespecified group of patients with significant electrical dysynchrony (QRS > 150 msec).
Echocardiography in dysynchrony
In her lecture, Dr Alison Duncan (Consultant Cardiologist, Royal Brompton Hospital, London) discussed the clinical effectiveness of various echocardiographic markers of ventricular dysynchrony, on response rates to CRT implantation. The PROSPECT (Predictors of response to CRT) trial was a large multicentre and prospective study evaluating the utility of various echocardiographic parameters of dysynchrony, based on M-mode, pulsed-wave Doppler and Tissue Doppler imaging (TDI). It concluded that the predictive value of such parameters was insufficient to influence clinical decision making.
Dr Duncan has studied global markers of dysynchrony, such as total isovolumic time (t-IVT), as part of a small retrospective single-centre study. She concluded that, global rather than segmental markers of ventricular dysynchrony may be more valuable predictors of response to CRT, though this has yet to be tested by a large prospective study.
Novel therapeutic strategies in heart failure
Anaemia in CHF
The need for checking haemoglobin and haematinics in patients with CHF, and correcting iron deficiency, where appropriate, was emphasised by Dr Klaus Witte (Honorary Consultant Cardiologist, Leeds General Infirmary, Leeds) in an epidemiological overview of anaemia in CHF. This is based on the findings of FAIR-HF (Ferinject Assessment in Patients with Iron Deficiency and Chronic Heart Failure), a large multicentre study, which showed benefit in various clinical end-points such as symptom limitation and quality of life, when comparing intravenous iron to placebo. The use of erythropoietin stimulating agents (ESAs) in CHF is more controversial. Whilst initial studies suggested improvements in LVEF, exercise capacity and quality of life, the randomised clinical trials that followed disappointingly did not show a significant benefit. Results of RED-HF (Reduction of Events with Darbopoetin-α in Heart Failure), a large mortality driven study are eagerly awaited.
Heart rate: the SHIFT study
Epidemiological and observational studies have shown that an elevated resting heart rate is a risk factor for mortality and poor cardiovascular outcomes. Professor Martin Cowie (Consultant Cardiologist, Royal Brompton Hospital, London) discussed this phenomenon and went on to look at the SHIFT (the Systolic Heart failure treatment with If inhibitor Ivabradine Trial) results, which showed a significant reduction in hospitalisation and death from HF when comparing ivabradine to placebo in patients with advanced HF on optimal therapy. Unsurprisingly, subgroup analysis suggested that those with higher resting heart rates derived greater benefit.
Sleep-disordered breathing conditions are prevalent in a staggering 50-60% of HF patients and Dr Anita Simonds (Consultant in Respiratory Medicine, Royal Brompton Hospital, London) gave a very insightful lecture on this area. These conditions can have adverse haemodynamic consequences for the failing heart. Studies have shown that CHF patients suffering from obstructive sleep apnoea (OSA) treated with continuous positive airway pressure (CPAP) have improved LVEF as well as a significantly reduced risk of death and hospitalisation.
CPAP has not shown any convincing evidence in the management of central sleep apnoea (CSA) associated with CHF. Dr Simonds did, however, talk about adaptive servoventilation (ASV), a novel ventilatory therapy which provides ventilatory support on detection of Cheynes Stokes respiration. A small randomised study has shown ASV to be of greater benefit than CPAP in treating CSA associated with CHF. We eagerly await the results of the SERVE-HF (Treatment of Sleep Disordered Breathing by Adaptive Servoventilation in HF patients) study, a large trial driven by mortality outcomes.
Exercise training in heart failure
Professor Andrew Clark (Honorary Consultant Cardiologist, Castle Hill Hospital, Hull) spoke about the importance of exercise training in the management of patients with CHF. He felt that skeletal muscle mass and function are more critical in determining exercise capacity than LVEF alone.
The safety and efficacy of exercise training in heart failure as compared to usual-care was evaluated in HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), a large, multicentre randomised controlled trial. Whilst there was no significant improvement in outcomes, a substudy of the trial did show a significant improvement in patient-reported health status as assessed using the Kansas City Cardiomyopathy Questionnaire.
Professor Clark went on to discuss his small pilot study involving training using electrical muscle stimulation in patients with HF who lead sedentary lifestyles. There may be a future role for therapies directed at skeletal muscle to improve HF symptoms, he concluded.
Heart failure in congenital heart disease
There is a growing problem of HF in adults with congenital heart disease. In an informative lecture, Dr Aisling Carroll (Consultant Cardiologist in GUCH, Southampton General Hospital, Southampton) said HF is now common in this population and is becoming increasingly prevalent even amongst patients with corrected defects as they are now surviving well into adulthood, owing to advances in cardiac surgery.
Dr Carroll presented cases using echocardiographic images to illustrate how failure develops in the chronically pressure overloaded systemic right ventricle, or in the volume overloaded subpulmonic right ventricle or in single ventricle physiology. Medical management of these patients is challenging as the anatomy and loading conditions of the heart are very different. Furthermore there are no large studies proving safety and efficacy of conventional therapies used in acquired HF. Dr Carroll therefore advocated adopting an individualised approach in the management of these patients.
The BSH medical training meeting is an ideal opportunity for cardiology trainees to gain a broad understanding of key issues in the management of heart failure from experts in the field. Interactive case presentations also delivered a number of key learning points useful for trainees in their everyday clinical practice. The informal and interactive structure of the day allowed for healthy audience participation, and it was particularly useful to learn how other clinicians approach common challenges encountered in the management of heart failure.
The meeting was co-organised by Dr Paul Kalra (Consultant Cardiologist, Queen Alexandra Hospital, Portsmouth) and Professor Iain Squire (Consultant Cardiologist, Leicester Royal Infirmary).
Cardiology Specialist Registrar
Queen Alexandra Hospital, Portsmouth