Heart failure is ejection fraction in motion

‘Everything changes but change itself. Everything flows and nothing remains the same… You cannot step twice into river, for other waters yet others go flowing ever on.’ Heraclitus of Ephesus, ∼500 BC. Well 21st century, left ventricular ejection fraction (EF) measurement continues to be mainstay classification patients with heart failure (HF). Although EF has many recognized limitations, it is easy obtain non-invasive, thus universally used HF stratification, surveillance, management. Clinical decisions are often based on a single value, in accordance results pivotal clinical trials recommendations international guidelines. However, several studies indicate that bidirectional transitions occur during course HF, potentially leading patient misclassification implement appropriate treatment.1 Following guidelines, have historically been classified as reduced (HFrEF) or preserved (HFpEF),2, 3 each group considered an exclusive unalterable compartment. In 2016, European Society Cardiology (ESC) guidelines officially adopted intermediate group, termed mid-range (HFmrEF; 40–49%).4 The 2021 universal definition includes HFrEF (EF ≤40%), mildly 41–49%), HFpEF ≥50%), improved (HFimpEF; baseline ≤40%, ≥10-point increase from EF, second >40%).5 This new guideline first introduce dynamic behaviour. current issue Journal, Strange et al.6 report largest study prognostic importance (up down) over long-term follow-up. authors retrospectively analysed patterns among ∼34 000 deaths >500 person-years surveillance ∼117 adults who had multiple measurements at intervals ≥6 months. main were one-third cases exhibited decline 5-unit was associated increasingly higher mortality. contrast, both stable increasing levels survival. Among 17 referred investigation, there clear gradient overall cardiovascular (CV) mortality across full spectrum EF. builds prior reports trajectories HFpEF.7-10 Moreover, unique important relevance due large number events, analysis upward downward changes. trajectory best studied all groups. Overall, follow-up, ∼50% continued show <40% (equal below EF), ∼25% HFmrEF, jumped (Figure 1A). forms inverted U-shape, lower ends distribution.7 data provided by follow-up CV mortality, while values survival benefit 1B). Extensive research explored whether improvement represents myocardial remission true recovery ‘myocardial cure’ HFrEF, which beyond scope present editorial comment. Since term HFmrEF introduced 2016 ESC guidelines,4 vast performed better characterize this (PubMed March 2021: 266 documents). evidence suggests not actually category itself, rather comprises EF.11 During around these remain trend HFpEF7 1C). Regarding outcomes sub-group, al. found slightly different trends compared HFrEF.6 As mortality; however, did up +10 units 1D). robust size, National Echo Database Australia (NEDA), observational database valuable ‘big data’ approach; unable provide granularity pathobiological insight such disparities. Most regarding longitudinal come retrospective analyses, subsequent assessments clinically driven susceptible indication bias.9, 10 also subject limitations. A recent prospective included pre-defined echocardiograms scheduled intervals, showed ∼88% remained ≥50% least decade ∼10% evolved <2% HFrEF8 1E). sub-group ischaemic aetiology, nearly 30% evolution prognosis relative dynamics heterogeneous may interpreted two sub-groups. 50–59%, similar those HFmrEF6 Indeed, sub-analyses designed examine spectrum, positive effect observed 60%, suggesting 50–59% range neurohormonal blockade, should further examined separate entity future trials. post-hoc Treatment Preserved Cardiac Function Heart Failure With Aldosterone Antagonist (TOPCAT) trial suggested potential efficacy spironolactone declining EF.12 Candesartan Failure: Assessment Reduction Mortality Morbidity (CHARM) trial, candesartan significantly primary outcome (CV death hospitalizations) ∼50%, recurrent hospitalizations ∼60%.13 More recently, putative placebo supported benefits sacubitril/valsartan most pronounced effects 60%.14 whose ≥60%, high flat regardless subsequently increased decreased. An only shown extreme changes6 1F). phenotype recently proposed ≥70% – supra-normal (HFsnEF) rates.15 introduction disease-modifying drugs quite unsuccessful, notable exception transthyretin amyloidosis. more personalized mechanistic approach improve situation. syndrome can disease progression, patient- aetiology-specific fashion. Current shows EF-based sub-groups overlapping than previously appreciated, dynamism implications. ever-changing nature will progressively incorporated design trials, recommendations. Conflict interest: none declared.