Just as general physicians have become accustomed to the concept of heart failure with preserved ejection fraction (HFpEF), the latest 2016 guidelines for the diagnosis and treatment of heart failure from the European Society of Cardiology (ESC) have introduced a new group of patients: those with heart failure with mildly reduced ejection fraction (HFmrEF).1 The ESC has explained that this new category was needed as a means to fill the gap that existed in the knowledge and understanding of heart failure as well as stimulating research on this group of patients who have not traditionally been included in studies on heart failure with reduced ejection fraction (HFrEF) or HFpEF.1 In the 2016 ESC guidelines, the diagnostic criteria for HFmrEF includes signs and symptoms of heart failure, an ejection fraction (EF) of 40–49%, elevated levels of natriuretic peptides and either relevant struc- tural heart disease (i.e. left ventricular hypertrophy and/or left atrial enlargement) or diastolic dysfunction observed during echocardiography.1 Interestingly, the last two criteria are also used to diagnose HFpEF; this new category could therefore be considered to constitute either pre-HFrEF or progressive HFpEF, assuming that HFpEF is a forerunner of HFrEF.2,3 This is supported by the fact that the ventricles of patients with HFpEF are not entirely normal and have certain contractile abnormalities.4,5 Previous Changes in Classifications In order to ascertain whether the new classification of HFmrEF is beneficial, it is useful to reflect on the introduction of the term ‘HFpEF’. Prior to the formal identification of this group of patients as a distinct entity, clinicians were aware that some patients, mainly elderly hypertensive females, presented with clinical signs of heart failure but displayed normal left ventricular function on echocardiography.6 Various aetiologies were suggested and these patients were initially labelled as having diastolic heart failure, as it was believed that these hypertensive patients had stiff ventricles that did not relax.6 In the absence of any Department of Medicine, Sultan Qaboos University Hospital, Muscat, Oman E-mail: sunilnadar@gmail.com abstract: The latest European Society of Cardiology (ESC) guidelines for the diagnosis and management of heart failure include a new patient group for those with heart failure with mildly reduced ejection fraction (HFmrEF). By defining this group of patients as a separate entity, the ESC hope to encourage more research focusing on patients with HFmrEF. Previously, patients with this condition were caught between two classifications—heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. Hopefully, the inclusion of new terminology will not increase confusion, but rather aid our understanding of heart failure, a complex clinical syndrome. Keywords: Heart Failure; Ventricular Ejection Fraction; Guidelines as Topic; Nomenclature. امللخ�ص: �ضملت املبادئ الت�جيهية االأخرية للرابطة االأوروبية لطب القلب لت�ضخي�ص وعالج ف�ضل القلب جمم�عة جديدة من ف�ضل القلب مع انخفا�ص قليل يف الك�رس القذيف. ح�ضب تعريف هذة املجم�عة من املر�ضى ككيان منف�ضل, تاأمل الرابطة االأوروبية لطب القلب ت�ضجيع املزيد من االأبحاث التي تركز على مر�ضى ف�ضل القلب مع انخفا�ص قليل يف الك�رس القذيف. �ضابقا, املر�ضى امل�ضاب�ن بهذا املر�ص كان�ا اإدراج اأن من ناأمل القذيف. الك�رس حفظ مع القلب ف�ضل و القذيف الك�رس انخفا�ص مع القلب الت�ضنيف-ف�ضل من ن�عني حتت يدرج�ن امل�ضطلح اجلديد لن يزيد من االإرتباك بل بالعك�ص �ضي�ضاعد على فهم ف�ضل القلب والذي يعترب متالزمة �رسيرية معقدة. الكلمات املفتاحية: ف�ضل القلب؛ الك�رس القذيف البطيني؛ املبادئ الت�جيهية كم��ض�ع؛ ت�ضمية. New Classification for Heart Failure with Mildly Reduced Ejection Fraction Greater clarity or more confusion? Sunil Nadar Sultan Qaboos University Med J, February 2017, Vol. 17, Iss. 1, pp. e23–26, Epub. 30 Mar 17 Submitted 15 Sep 16 Revision Req. 31 Oct 16; Revision Recd. 21 Nov 16 Accepted 8 Dec 16 doi: 10.18295/squmj.2016.17.01.005 SOuNDINg bOARD New Classification for Heart Failure with Mildly Reduced Ejection Fraction Greater clarity or more confusion? e24 | SQU Medical Journal, February 2017, Volume 17, Issue 1 clinical evidence, clinicians often treated this group of patients in the same way as those with HFrEF, with varying results.7 It was Gandhi et al. who first reported 38 patients presenting with hypertensive acute pulm- onary oedema and preserved left ventricular func- tion, both during the acute phase and after success- ful treatment of their acute presentation, thus demo- nstrating that these patients constituted a distinct entity.8 This patient group was subsequently given many labels, such as ‘diastolic heart failure’ and ‘heart failure with normal EF’.9 Eventually, the American Heart Association and the ESC formally accepted the term ‘HFpEF’.10,11 The formal recognition of HFpEF as a distinct entity has led to more focused research on this group of patients. It is now known that these patients are a heterogeneous group not limited to elderly hyper- tensive females and whose ventricles have normal systolic function with varying degrees of stiffness and diastolic abnormalities.12 In addition, evidence now shows that many of the treatment modalities for treating HFrEF are ineffective for patients with HFpEF.12 These findings have changed the manage- ment of and approach to dealing with patients with HFpEF, although there are admittedly still many unanswered questions.13 In a similar manner, despite the possible initial reluctance to accept another category of heart failure patients, the decision by the ESC to define HFmrEF may help to increase understanding of this disease and improve its treat- ment, particularly for patients who fall in between the two previous categories. Current Approaches to Diagnosis and Management Clinicians familiar with the management of heart failure patients will know that individuals with HFmrEF are often difficult to treat. In a way, they are somewhat similar to HFpEF patients whereby the symptoms of heart failure appear disproportional to the level of reduced EF; moreover, these patients do not often respond as well to diuretics, angiotensin- converting enzyme inhibitors or β-blockers.14 Similar to the treatment that HFpEF patients received prior to breakthroughs in the understanding of the disease, HFmrEF patients are still treated with similar management plans to those of HFrEF patients.15 Although there is often no evidence to back up these management plans, clinicians tend to rely on their clinical experience. Perhaps time will tell whether these patients are more likely to respond to conven- tional heart failure treatments or whether there is a need for more specific treatment modalities. Currently, the ESC guidelines have combined the management of patients with HFmrEF with that of HFpEF patients.1 A major problem in the management of HFpEF, and now HFmrEF as well, is establishing the diag- nosis.16 There is still some reluctance to label a patient with preserved left ventricular function as having heart failure; as such, HFpEF and HFmrEF patients are often underdiagnosed.16 These patients sometimes undergo multiple tests to rule out respiratory and ischaemic causes of breathlessness before ultimately being diagnosed with heart failure. Moreover, HFpEF and HFmrEF patient groups are heterogeneous and often have multiple comorbidities that can confuse the diagnosis.12 There is a danger of both the over- and underdiagnosis of heart failure. Epidemiological studies have shown that the incidence of HFpEF appears to be on the rise.17,18 This could potentially be explained by the developing awareness of HFpEF on the part of clinicians and their increased willing- ness to make this diagnosis now that it has been officially recognised. Opportunities for Further Research With the previously undefined group of HFmrEF patients now having been legitimised with an official name, albeit one difficult to articulate properly, it can be hoped that this will spur research focusing specifically on this patient group.19 Currently, it is unknown whether these patients have a milder version of HFrEF, if HFmrEF indicates those with HFpEF whose EF is now deteriorating or indeed if it is simply a part of the heart failure continuum.19 Along those lines, it is not clear whether aggressive treatment of HFpEF would prevent patients from progressing to HFmrEF or whether aggressive management of HFmrEF would prevent patients from deteriorating to HFrEF. More research is therefore justified. This change in nomenclature gives rise to many questions that clinicians have perhaps always asked themselves, but never had the chance to openly query; these can hopefully now be answered, perhaps via large-scale clinical trials. Alternative Classifications of Heart Failure It must be noted that the use of EF as a method of classifying heart failure is not universally agreed upon. De Keulenaer et al. argue that HFpEF and HFrEF are overlapping phenotypes within the spectrum of heart failure and that the use of EF to classify heart failure is Sunil Nadar Sounding Board | e25 not accurate.3 They suggest that this classification came about primarily because early heart failure drug trials included patients with low EF, who were considered a high-risk group, in order to produce statistically significant results.3 Subsequently, an emphasis on evidence-based medicine has automatically led to the use of cut-off values derived from the results of these trials. Another suggestion is that the disease be classified based on aetiology or physiological abnormalities, as well as the clinical presentation of acute or chronic heart failure symptoms, as this affects management choices.9 Furthermore, by using pathophysiology to classify heart failure, other researchers have proposed the use of biomarkers either alone or in combination with echocardiography in order to guide therapy and management choices, instead of relying entirely on EF measurements.20–22 Conclusion Despite the announcement by the ESC of yet another category of heart failure patients with a tongue- twisting acronym, it is unlikely that the clinical management of this new HFmrEF patient group will change immediately. However, this new classification does define another subset of heart failure patients on whom additional and more focused research can now be conducted. 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Troughton RW, Frampton CM, Brunner-La Rocca HP, Pfisterer M, Eurlings LW, Erntell H, et al. Effect of B-type natriuretic peptide-guided treatment of chronic heart failure on total mortality and hospitalization: An individual patient meta-analysis. Eur Heart J 2014; 35:1559–67. doi: 10.1093/ eurheartj/ehu090. 21. Troughton R, Michael Felker G, Januzzi JL Jr. Natriuretic peptide-guided heart failure management. Eur Heart J 2014; 35:16–24. doi: 10.1093/eurheartj/eht463. 22. Simioniuc A, Carluccio E, Ghio S, Rossi A, Biagioli P, Reboldi G, et al. Echo and natriuretic peptide guided therapy improves outcome and reduces worsening renal function in systolic heart failure: An observational study of 1137 outpatients. Int J Cardiol 2016; 224:416–23. doi: 10.1016/j. ijcard.2016.09.034.