‘All you need to know about heart failure – in one day’ was the promise of the 10th British Society for Heart Failure day for revalidation and training held on 19th June 2018 in Birmingham. The day provided a whistle-stop tour through the landscape of heart failure including drugs, devices, comorbidities, revascularisation and transplantation. Dr Andrew D’Silva reports some of the highlights.
Drug therapy
From treating dropsy…
Treating congestion is an essential role of the heart failure specialist with diuretic therapy being the cornerstone of treatment. There is an evidence vacuum, however, in how best to relieve congestion. For example, which agents to use, at what doses and with what escalation strategy? Dr Peter Cowburn (Southampton General Hospital) delivered an exemplary lecture highlighting the importance of relieving congestion, the current evidence base and practical advice from his personal experience on how best to achieve the goal of euvolaemia.
Relieving congestion matters and, when achieved, is associated with lower mortality but a common concern is whether renal function will tolerate escalating doses of diuretics. It is often a reason for holding back or suspending angiotensin converting enzyme (ACE) inhibitors or mineralocorticoid receptor antagonists (MRAs). The message was clear: be not afraid! On one hand, renal impairment often improves with appropriate diuresis due to reduction in renal venous pressure, renal arterial vasodilatation mediated by reduced sympathetic innervation and resultant improvement in glomerular filtration. On the other hand, should serum urea and creatinine levels rise with diuretic therapy, do not be discouraged.
Contemporary studies suggest that relieving congestion and maintaining heart failure therapies matters more than some deterioration in renal function. Dr Cowburn shared the benefit of his experience with his personal tips for clinical practice. This included a critique of CARRESS-HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure),1 which demonstrated that ultrafiltration is not superior to standard diuretic care, provided that higher doses are administered when required and aggressive diuresis is generally safe.
…to PARADIGM-shifting therapies
Moving to an area rich in evidence-based medicine, Dr Lisa Anderson (St George’s Hospital, London) provided a comprehensive and valuable review of ACE inhibitors, angiotensin receptor blockers (ARBs) and when to introduce the angiotensin receptor blocker/neprilysin inhibitor (ARNI), sacubitril/valsartan. Combination therapy to improve prognosis in heart failure with reduced ejection fraction (HFrEF) has now been well established for over 30 years. The mortality benefit in clinical trials demonstrated by ARBs is less consistent than with ACE inhibitors and practice has changed since some of those trials were conducted, when ARBs and ACE inhibitors were combined. Considerably less evidence exists for benefit in heart failure with preserved ejection fraction (HFpEF) but in the HFrEF population a wealth of data support ACE inhibition to be the foundation of prognostic heart failure therapy.
The PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity Heart Failure) study2 has been a welcome development, providing us with another life-saving heart failure therapy and potentially redefines optimal pharmacological heart failure therapy as a package without an ACE inhibitor. Before rushing to switch your patients, however, Dr Anderson provided a careful review of the trial design and practical advice on selecting patients most likely to benefit and tolerate sacubitril/valsartan. In essence, patients closely matching the trial inclusion criteria, for example: systolic blood pressure over 100 mmHg, potassium level less than 5.2 mmol, and estimated glomerular filtration rate greater than 30 ml/min/1.72m2, will generally avoid situations where sacubitril/valsartan is poorly tolerated. Excessive restriction, however, may also promote underutilisation, which has been suggested by low initiation rates after drug approval.
Professor Theresa McDonagh (King’s College Hospital, London) delighted in sharing why beta blockers and MRAs are “a few of her favourite things”, though without breaking into song! Why should all heart failure specialists wax lyrical about these agents? The answer lies in the magnitude of mortality reduction they provide in HFrEF, albeit in combination rather than in competition with ACE inhibitors.
The lecture covered in detail which, when, and in whom, these medications best serve, supported by a wealth of presented clinical trial data. Whilst the choice of beta blockers is ample, only three are licensed and available for the treatment of HFrEF in the UK: carvedilol, bisoprolol and nebivolol. That is not to say that agents like propranolol or timolol are harmful. Professor McDonagh provided some reassuring advice that patients thriving on these agents are likely to benefit from a beta-blocker class effect and, if well-established, one should avoid switching. The formulation of metoprolol efficacious in heart failure is not available in the UK. With respect to bisoprolol, dose matters and evidence of benefit exists above doses of 5 mg daily. The evidence for MRAs was showcased highlighting that spironolactone had more evidence of benefit in severe heart failure and eplerenone more data post-myocardial infarction, with men experiencing less gynaecomastia.
Cardiac resychronisation therapy: cui bono?
Personalising heart failure care and selecting patients who will benefit from therapies is a critical part of the specialty and avoids exposing patients to unnecessary risk for little or no gain. The arena of devices in heart failure exemplifies this predicament with a myriad of clinical studies to amalgamate into clinical decision-making. In fact, as Dr Francisco Leyva (Queen Elizabeth Hospital, Birmingham) elegantly underlined in his learned talk, real-world patients are often more complex with many groups under-represented in the landmark trials that support the use of cardiac resynchronisation therapy (CRT).
Such groups include those with renal failure, severe tricuspid regurgitation and valve replacements, who tend to respond less well to CRT but that is not to say that all individuals in these groups will not benefit. Whilst the CRT non-responder rate is approximately 30%, Dr Leyva reminded the audience that any therapy assessed to this standard, such as chemotherapy for cancer, would view a 70% responder rate as a resounding success and therefore not a reason to be disheartened.
Although patients with a left bundle-branch block ECG, typically respond better, in most cases of right bundle-branch block, there tends to be an element of partial left bundle-branch block that will respond to CRT. As such, the pattern of bundle-branch block is less important in selecting suitable patients but what is apparent is that the wider the QRS complex, the greater the likelihood of response. A QRS duration of 130 ms represents the graphical point corresponding to a hazard ratio of one and so becomes the threshold above which the majority will benefit.3
Response to CRT can improve pulmonary haemodynamics, pulmonary capillary wedge pressures, promote biventricular remodelling and potentially reduce the severity of mitral regurgitation. Valvular interventions increase the need for pacing therapy when conduction is disturbed. Dr Leyva, however, drew attention to his own research findings demonstrating that patients with post-surgical valvular, non-ischaemic cardiomyopathy experience worse outcomes with CRT, when compared to idiopathic dilated cardiomyopathy. This is potentially driven by a higher rate of pump failure deaths.
Co-morbidities: heart failure and AF – partners in crime
A recurring theme over the day was the impact of atrial fibrillation (AF) on heart failure, which from a clinical standpoint are easy bedfellows. AF potentially influences the efficacy of beta blockers, interferes with CRT biventricular pacing and eliminates any potential benefit from ivabradine. For some time the cardiologist has looked at the heart failure patient with a dilated, fibrillating left atrium and perceived little chance of achieving lasting sinus rhythm. When one considers the possible complexity of the underlying atrial substrate, the requirement for extensive ablation often beyond pulmonary vein isolation alone, and the risk of complications including introduction of atrial tachycardias, there is understandable inertia to undertake such procedures in this population.
Dr David Jones (Harefield Hospital, London) takes an opposing stance and delivered an impassioned lecture strongly advocating a greater consideration of catheter ablation in heart failure patients. Beginning by impressing upon the audience that the contribution of atrial contraction to cardiac function is considerable and heart failure patients may stand to gain the most, Dr Jones went on to make his case through persuasive interpretation of the available clinical trial data, including the recent CASTLE-AF (Catheter Ablation versus Standard Conventional Therapy in Patients with Left Ventricular Dysfunction and Atrial Fibrillation) study.4 In doing so he highlighted some very important considerations, limitations and gaps in our current knowledge on the subject. Firstly, assessment of left ventricular ejection fraction, as a key parameter in assessing cardiac function, is subject to considerable variation in the presence of AF and therefore a poor indicator of treatment success. The extent to which tachycardia-related cardiomyopathy exacerbates cardiac dysfunction is generally underappreciated and efforts to address reversible components and reassess are worthwhile. In summary, AF and heart failure coexist in an electromechanical cycle and catheter ablation is an effective but underutilised tool in increasing time in sinus rhythm.
Coronary revascularisation: a STICH in time?
Revascularisation and viability assessment in heart failure continue to stimulate heated debates in joint cardiothoracic and cardiology meetings around the world regarding the relative merits of coronary artery bypass graft surgery (CABG), stents or medication alone. Professor Mark Petrie (Golden Jubilee National Hospital, Glasgow) took on this mammoth issue and delivered a machine-gun paced exposition on revascularisation in heart failure, laying to waste any misconceptions that prior observational data were sufficient to support revascularisation “on prognostic grounds”.
Now with the 10-year follow-up results of the STICH (Surgical Treatment for Ischemic Heart Failure)/STICHES (Extension Study) trial,5 there is greater clarity on the comparison of CABG and medical therapy only. In the first two years, mortality is higher with surgery, likely related to the early surgical risks/complications. At five years, the mortality in the medical therapy group catches up with no difference in outcomes but at 10 years, mortality is lower with CABG. Forecasting which patients will live long enough to benefit and survive the surgical insult remains a clinical challenge and prompts a question to the interventional cardiology community: can stents provide a similar benefit with lower risk of harm? No data currently exist to support this but trials are underway to answer this question and Professor Petrie made a far-reaching plea to refer patients to centres participating in the REVIVED-BCIS2 (Revascularisation for Ischaemic Ventricular Dysfunction) trial (NCT01920048),6 as such trials historically suffer from under-recruitment.
With respect to whether all patients need a coronary angiogram, this is a subject of ongoing debate and generated provocative discussion. Whilst knowledge of the underlying heart failure aetiology assists with considering treatment options and prognosis, coronary angiography may not be essential. Many in the audience favoured cardiac magnetic resonance imaging to investigate aetiology and potentially inducible ischaemia. More studies are required to assess whether such a strategy improves outcomes, is cost-effective and feasible on a UK-wide scale.
Heart transplantation and mechanical circulatory support in the current era
Heart transplantation celebrates its remarkable 50th year as a life-saving intervention for advanced heart failure and the UK boasts seven cardiothoracic organ transplantation centres. The final talk of the day was introduced with a highly illustrative clinical case outlining the extensive work up required in heart transplantation assessment, the challenges faced by a patient supported by intravenous inotropic agents on the urgent waiting list, and when short- and long-term mechanical circulatory support devices are required to bridge a patient to transplantation.
Dr Sern Lim (Queen Elizabeth Hospital, Birmingham) followed with an excellent talk updating the audience on the current state of play in the field of heart transplantation and left ventricular assist devices (LVAD). Heart transplantation patients currently have a median life expectancy of 11 years with 85–90% survival at one year. Emphasis was placed on the comprehensive assessment process allowing specialists to best assess what the prognosis is on conventional heart failure therapies and whether the outlook could be improved with heart transplantation, provided no contraindication is present.
Dr Lim presented some sobering statistics from a smorgasbord of clinical trials including drugs, devices, catheter ablation and surgery undertaken in heart failure patients, in order to illustrate the frequent underestimation of mortality in the heart failure population and how the benefits of such interventions are often overestimated. By comparison, heart transplantation and LVAD therapy risks are often perceived to be higher than the reality and as these treatments improve prognosis, functional capacity and quality of life, referral should be considered earlier. This point resonated with the entire faculty who emphasised that there is no shame in referring patients who turn out to be “too good for transplantation at the present time”.
In conclusion, the meeting educated on a number of key topic objectives including: choices in effective pharmacotherapy, comorbidity management, contemporary use of complex devices and optimal patient selection for advanced heart failure therapies. The resounding success of the meeting emanated from the engaging and enthusiastic panel of expert speakers, combined with the efforts of all those involved.
Acknowledgment
The BSH gratefully acknowledges the support provided by the Friends of the BSH: Abbott, AstraZeneca, Bayer, Boston Scientific, Medtronic, Novartis Pharmaceuticals, Roche Diagnostics and Vifor Pharma.
Diary dates
Future BSH meetings will be held on:
- 29th–30th November 2018: 21st BSH Annual Autumn Meeting, QE II Centre, London
- 26th March 2019: 11th Heart Failure Day for Revalidation and Training, Golden Jubilee Conference Centre, Glasgow
- 27th March 2019: Heart Failure Nurse and Healthcare Professional Study Day, Golden Jubilee Conference Centre, Glasgow
For further information, contact the British Society for Heart Failure, “Nought” The Farthings, Marcham, Oxfordshire, OX13 6QD.
Tel: 01865 391836, e-mail: [email protected], website: www.bsh.org.uk, Twitter: @BSHeartFailure
Andrew D’Silva
Cardiology Specialist Registrar
Royal Sussex County Hospital, Brighton ([email protected])
References
1. Bart BA, Goldsmith SR, Lee KL, et al. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med 2012;367:2296–304. https://doi.org/10.1056/NEJMoa1210357
2. McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993–1004. https://doi.org/10.1056/NEJMoa1409077
3. Leyva F, Nisam S, Auricchio A. 20 years of cardiac resynchronization therapy. J Am Coll Cardiol 2014;64:1047–58. https://doi.org/10.1016/j.jacc.2014.06.1178
4. Marrouche NF, Brachmann J, Andresen D, et al. Catheter ablation for atrial fibrillation with heart hailure. N Engl J Med 2018;378:417–27.
5. Velazquez EJ, Lee KL, Jones RH, et al. Coronary artery bypass surgery in patients with ischemic cardiomyopathy. N Engl J Med 2016;374:1511–20. https://doi.org/ 10.1056/NEJMoa1707855
6. Perera D, Clayton T, Petrie MC, et al. Percutaneous revascularization for ischemic ventricular dysfunction: rationale and design of the REVIVED-BCIS2 trial: percutaneous coronary intervention for ischemic cardiomyopathy. JACC Heart Fail 2018;6(6):517–26. https://doi.org/10.1016/j.jchf.2018.01.024
