We have great pleasure in introducing the second volume of Cardiac Failure Review to our readers. In recent weeks we have attended innovative conferences that have highlighted new devices that show great promise in heart failure treatment, one in Brussels, Belgium that coincided with the tragic events there, and one in Seoul, Korea – an impressive emerging Asian superstar.
In heart failure news, the UK’s NICE committee has recommended the combination agent sacubitril–valsartan (LCZ696) for rapid uptake by the NHS. This follows US Food and Drug Administration and European Medicines Agency approval.
We also await with great anticipation the launch of the 2016 European Society of Cardiology/Heart Failure Association guidelines for the diagnosis and treatment of acute and chronic heart failure at the Heart Failure Association meeting in Florence, Italy. This is the first update of these important guidelines since 2012 and we wait to see how pivotal studies such as the Echo-CRT (Echocardiography Guided Cardiac Resynchronization Therapy)1 and PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure)2 studies have altered the recommendations. It is an exciting time in heart failure globally.
In this issue we have leading experts review a crucial list of subjects relevant to the practising heart failure specialist and interested generalist alike.
Martinez-Dolz and colleagues review novel imaging techniques in heart failure. Of course, echocardiography emerges as the investigation for the majority of heart failure assessment. Its familiarity, safety, low cost and availability make it an essential tool for any cardiologist. Long gone are the days when you could manage a patient without this tool. It is a must for all patients at some stage in the clinical journey, and indeed can be used repeatedly to assess response to therapy, and to assess the likelihood of responding to certain therapies. They also review more advanced imaging options including cardiovascular magnetic resonance (CMR), nuclear imaging-positron emission tomography, single-photon emission computed tomography and computed tomography (CT). The authors update us on new techniques in echocardiography such as 3D echocardiography and myocardial contrast enhanced echocardiography3 and the more sensitive measure of systolic function that can be gained by measuring global longitudinal strain, usually assessed by speckle-tracking echocardiography.4 This appears to be gaining acceptance as a sensitive way of monitoring left ventricular systolic function in patients receiving potentially cardiotoxic anticancer chemotherapy.5 They also review the advantages of accurate left atrial imaging and assessment.6,7
In the section on CMR, we are updated of the added value of late gadolinium enhancement patterns, which provide diagnostic utility for distinguishing between ischaemic and non-ischaemic cardiomyopathy,8 and to predict viability and recovery of contractile function after revascularisation.9,10 There is also a valuable update on the growing role of multi-detector CT, as well as hybrid imaging techniques that combine the advantages of multiple modalities.
Tamargo Menendez reviews the most significant advance in the therapy of chronic heart failure for a decade: the demonstration that LCZ696 (the combination of the neprilysin inhibitor, sacubitril, with an angiotensin II receptor blocker, valsartan) is more effective than the angiotensin converting enzyme (ACE) inhibitor, enalapril. The PARADIGM-HF trial showed that LCZ696 significantly reduced CV death or HF hospitalisation (20 %; p<0.001), CV death (20 %) and all-cause mortality (16 %), versus enalapril.2 This review covers the modes of action of this exciting new combination drug therapy, however reports of poor uptake suggest concern about the narrow inclusion criteria of this single trial, limiting the comparability of the PARADIGM-HF population and other chronic heart failure patients.
Hayman and Atherton take up the theme by asking whether this new agent – coined an angiotensin receptor neprilysin inhibitor (ARNI) – should routinely replace ACE inhibitors in the management of heart failure with a reduced ejection fraction (HFrEF). They review the added value of neprilysin inhibition when added to blockade of the adverse effects of angiotensin II in HFrEF.
Hayman and Atherton also remind us that neprilysin is an enzyme that catalyses the degradation of a number of vasoactive compounds, including natriuretic peptides, and that natriuretic peptides have multiple actions that could have a favourable effect on heart failure disease progression, including vasodilation, natriuresis and diuresis11 – a topic taken up in more detail in the excellent review by Lee and Daniels, also in this issue. This reasoning suggests inhibition of neprilysin may add therapeutic benefit, despite the fact that the mimetic, nesiritide, had no effect on death or rehospitalisation rates in the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) study.12 This may indicate there is something special about sacubitiril, or that the different heart failure syndromes – HFrEF, heart failure with preserved ejection fraction13 and acute heart failure – are simply too different to be treated in the same way. Hayman and Atherton argue that PARADIGM-HF is the only trial supporting the use of ARNI over ACEI in patients with HFrEF, but that nonetheless this was a large study primarily powered to detect a difference in cardiovascular mortality, which it convincingly showed. They hold that the most appropriate population to receive ARNI in clinical practice would match those who were studied in the PARADIGM-HF study, namely patients with symptomatic HFrEF despite appropriate doses of ACEI (or ARB) and beta-blockers. They concentrate our attention on the exclusion criteria, ways in which the potential target population can be whittled away to a non-representative subset of HFrEF. These included hypotension, estimated glomerular filtration rate <30 ml/min/1.73 m2 of body surface area, hyperkalaemia, a history of angioedema or unacceptable side effects from ACEI or ARB and anyone intolerant to forced up-titration of either LCZ696 or enalapril to quite high doses. Therefore, they argue to restrict LCZ696 in favour ACEI or ARB therapy in patients without symptomatic hypotension or systolic blood pressures <95–100 mmHg.
Fauchier and colleagues discuss the surprisingly topical issue of whether beta-blockers or digoxin should be used for atrial fibrillation in heart failure. Surprising because we thought we had answered these questions in major trials nearly two decades ago. They review the very live debates on a possible reduced efficacy of beta-blockers in HFrEF patients in atrial fibrillation following the recent impressive individual patient data meta-analysis that analysed the total body of evidence for a prognostic role of beta-blockers in this setting and concluded there was none.14 They also review recent safety concerns over digoxin use in treating HFrEF patients with atrial fibrillation. They conclude that the benefit of beta-blockers on survival may be lower in patients with HFrEF when atrial fibrillation is present and that digoxin does not improve survival, but may help to obtain satisfactory rate control in combination with a beta-blocker; and that digoxin may also be useful in the presence of hypotension or an absolute contraindication to betablocker treatment in HFrEF with background atrial fibrillation.
We also highly recommend the review on cardiac rehabilitation in chronic heart failure by one of the pioneers of this field, our expert colleague Volterrani, and Iellamo, and the review by Alzahri, Rohra and Peacock on the role of nitrates in the treatment of acute heart failure. Last, but certainly not least in importance, there are excellent reviews by Anthony and Sliwa on decompensated heart failure in pregnancy; Rudiger and colleagues on the management of what they describe as “the silver days” – intensive care management beyond the 6 hours of cardiogenic shock; and Fragasso on the role of deranged cardiac metabolism in the pathogenesis of heart failure and potential interventions to improve outcomes by targeting this mostly universal but largely ignored aspect of chronic heart failure pathophysiology.
We hope you will enjoy reading this issue as much as we enjoyed helping assemble it.