CFR 4.2 by Radcliffe Cardiology

Foreword

Andrew JS Coats is the inaugural Joint Academic Vice-President of Monash University, Australia and the University of Warwick, UK and Director of the Monash Warwick Alliance

Giuseppe Rosano is Professor of Pharmacology, Director of the Centre of Clinical and Experimental Medicine at the IRCCS San Raffaele, Italy and Professor of Cardiology and Consultant Cardiologist (Hon) at St George's University of London, UK

t is with great pleasure that we introduce to you, our readers, Volume 4.2 of Cardiac Failure Review. Heart failure with mid-range ejection fraction, HFmrEF, formally introduced into the definition of heart failure phenotypes by the 2016 ESC Heart Failure Guidelines,1 has been the subject of intense investigation and analysis since its launch as a concept. One of these outcomes has been the re-analysis of existing clinical trial databases to establish what treatments can be said to be effective also in HFmrEF in addition to HFrEF. Although what we would like are prospective randomized controlled trials specifically designed to test the hypothesis that a particular treatment would beneficially effect HFmrEF, such trials are unlikely to occur soon, if at all. Until then, the best we can get is detailed analysis of individual patient data, including all outcome trials that included HFmrEF patients without bias. In this issue, Lars Lund of Stockholm explores evidence from the CHARM programme of the effectiveness of Candesartan Cilexetil in the therapy of HFmrEF. In a recently published analysis,2 Lund and colleagues showed the effect of Candesartan when used to treat HFmrEF. He

summarised data from observational studies and registries suggesting the prevalence of HFmrEF out of all heart failure (HF) subtypes varied between 10 and 24%. This HFmrEF cohort similarly comprised 17% of the CHARM programme, showing it was within the range of what is seen in the community. In CHARM, despite lower mortality rates in HFmrEF compared to HFrEF, the primary outcome for candesartan versus placebo was similar with a hazard ratio (95% confidence interval) of 0.82 (0.75–0.91, p<0.001) in HFrEF compared to 0.76 (0.61–0.96), p=0.02) in HFmrEF, which was distinctly different to what was seen in HFpEF (0.95 [0.79–1.14] p=0.57). Similar results were seen for recurrent HF hospitalization, with incidence rate ratios of 0.68 (0.58–0.80, p<0.001) for HFrEF and 0.48 (0.33–0.70, p<0.001) for HFmrEF, compared to 0.78 (0.59–1.03, p=0.08) for HFpEF. Taken together with similar analyses for beta-blockers3 and a subgroup report of the effect of spironolactone in TOPCAT,4 this is beginning to suggest that HFmrEF should be treated the same as HFrEF, albeit noting that the evidence for spironolactone is considerably weaker than the other two, because it is a sub-analysis of a single trial, and one that itself was not statistically significant for benefit as designed. We have an article from the Cleveland Clinic that reviews modern advances in imaging in heart failure. The authors stress developments they see emerging in modern imaging in HF. They predict an expansion of the use of echocardiography in assessing two aspects of importance in modern HF management: diastolic function and exercise-induced changes in ventricular function. They also update us on the usefulness of multi-detector computed tomography and cardiovascular magnetic resonance. They offer a review of what they coin “molecular imaging”, in which radionuclide imaging, using either positron emission tomography (PET) or single-photon emission computed tomography, can be used for characterization of tissue function in myocardial disorders, including 123I-labeled MIBG, as a marker of adrenergic function to risk stratify patients for risk of ventricular arrhythmic sudden cardiac death (SCD), and the progression of HF autonomic dysfunction. Another important area is the accurate assessment of coronary flow reserve with stress myocardial perfusion PET. Lastly, they introduce the exciting future world of hybrid imaging and 3D printing. Cardiac hybrid or fusion imaging combines imaging modalities to enhance functional and structural detail, as well as helping guide interventional procedures with immediately updated images peri-procedure. Based on hybrid imaging, and with the addition of advanced polymer technologies to make realistic tissue “feel”, 3D printing may in future allow careful planning of complex procedures, and aid in teaching and objective credentialing of practical competence in procedures. We have two articles on the emerging field of the heart–brain–nerve axis in HF. Scherbakov and Doehner review heart–brain interactions in HF, such as the effects of HF on the brain, including cardio-embolic and low perfusion pressure effects, the impairment of higher cortical and brain stem functions (cognitive impairment, sympathetic over-activation, neuro-cardiac reflexes), as well as treatment-related interactions, including drug- and device-related interactions. Peter Hanna and colleagues at the UCLA Neurocardiology Program review the field of autonomic reflex targeted therapies for HF. HF is characterized by significant and potentially mechanistically important DOI: 10.15420/cfr.2018.4.1.FO1

Access at: www.CFRjournal.com

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