The path to universality

This article refers to ‘Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure Consensus Conference. Endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, Chinese Heart Failure Association’ by B. Bozkurt et al., published in this issue on pages 352–380. Forty years after William Harvey's monumental discovery of the circulation in 1628, Richard Lower, an Oxford physician, provided one of the first descriptions of heart failure (HF). He stated that ‘when the heart lacks the strength to preserve a consistent circulation of the blood… the parenchyma of the heart… suffers from inflammation, ulcer, abscess… so that it is unable to pulsate and contract without great difficulty.’1 Since then there has been progress in every aspect of HF – diagnosis; pathogenesis; improved understanding of the interplay between haemodynamic, biochemical, biomarker, genomic, and epidemiologic aspects of HF. Treatment has improved enormously, especially in the last 50 years (Figure 1). An essential component of the trials that led to these recent advances was a clear definition of HF in the populations studied. There is a long and distinguished history of efforts to define HF, only a sample of which is presented here (Figure 1). In 1921, exactly one century ago, Paul Dudley White, widely considered to be the father of American Cardiology, published a classification of cardiac diagnosis in which he described four levels of activity which classified the physical capacity of patients with HF.2 In 1928, these levels were renamed functional classes by the New York Heart Association.3 These have been updated4 and continue to be widely used to detect and quantify changes in the severity of symptoms at rest and on exertion in patients with HF. In 1971, McKee and colleagues in the Framingham Heart Study published specific clinical criteria for the diagnosis of HF, which also form the basis of more recent definitions.5 In 2001 the American College of Cardiology (ACC)/American Heart Association (AHA) introduced four stages of HF which incorporated risk factors for the development of HF and the changes in the structure and function of the failing heart.6 In 1995 a task force on HF of the European Society of Cardiology (ESC) published guidelines for the diagnosis of HF7 which went beyond symptoms but also required objective evidence of cardiac dysfunction in the definition. In 1999, the Heart Failure Society of America (HFSA) published its first HF practice guidelines8 which have been updated several times. In 2016, one of the authors of this editorial (EMA) and colleagues emphasized the importance of achieving an international alignment of HF guidelines on behalf of the ACC, AHA, and the ESC in collaboration with the HFSA and the Heart Failure Association (HFA) of the ESC. This was an effort to get the three largest and most active cardiac societies in the world to coordinate the messages of their respective organizations to improve and standardize patient care.9 This represented the first formal attempt to develop international guidelines and definitions of HF, an important step on the path to universality. Notably, the guidelines for the treatment of HF by the ACC/AHA in 201310 and the ESC in 201611 included detailed summaries of the definition and classification of HF. Most recently, in December 2020, the Academic Research Consortium convened leading HF academic investigators (which included five co-authors of the current paper), as well as representatives of the US Food and Drug Administration (FDA), patients with HF, and industry members from the US and Europe to provide ‘Standardized Definitions for Evaluation of HF Therapies.’12 The major strength of the present report13 lies in the experience, thoughtfulness, and leadership of the authors. It is substantially more comprehensive than its many predecessors. For example, it includes useful discussions of topics such as the relationship between HF and cardiomyopathy, myocardial infarction (MI), and cardiogenic shock. It also deals with right ventricular failure, as well as high-output HF. It places appropriate emphasis on the changes of HF trajectories that often occur, as well as the possibility of recovery from HF. The report appropriately gives natriuretic peptides a prominent role in the definition, along with structural and functional abnormalities of the heart. The role of natriuretic peptides is more challenging than a comparable one for the use of cardiac-specific troponins in the universal definition of MI.14 Troponins are central to the diagnosis of MI, while elevated natriuretic peptides are supportive of the diagnosis of HF; the latter are more indicative of the severity of the underlying myocardial abnormality, but have a lower specificity for HF than troponin has for MI. The definition and classification of HF presented in this report have three basic components. The first, that defines HF as a syndrome and lists its symptoms and signs, was well established by the Framingham Group in 1971,5 although the listing of symptoms and signs of HF are now more comprehensive. The specific structural, functional and/or natriuretic peptide abnormalities required to establish the diagnosis of HF and the need for corroboration are useful additions. The second component maintains the four stages of HF proposed by the ACC/AHA6 but recommends important changes in terminology. The current report points out correctly that patients in stages A and B do not have HF; instead we agree that the terms ‘at risk for HF’ and ‘pre-HF’, respectively, are more appropriate. The third component of the definition supports the growing practice to categorize HF by multiple levels of ejection fraction, with the mid-range ejection fraction ranging from 41% to 49%. The first section of the current report,13 in our opinion, may be unnecessarily critical of earlier definitions of HF. For example, statements such as: ‘Currently available definitions of HF are ambiguous and lack standardization’ were taken out of context. The earlier definitions, while outdated at present, were appropriate at the time of release. When some of the earlier definitions were prepared, natriuretic peptides had not yet been discovered or were not widely available. These earlier definitions were, however, good enough to identify patients who, when enrolled into clinical trials, exhibited the spectacular advances in the management of patients with HF. When criticizing the past it is well to recall Isaac Newton's statement: ‘If I have seen further, it is by standing on the shoulders of giants.’15 While the authors have entitled this report as ‘Universal definition and classification’ of HF, in the text they also refer to it as a ‘proposed universal definition…’ The goal of developing a ‘universal’ definition is admirable, but in our opinion has not yet been achieved. The present consensus document should undergo rigorous review, validation, and ‘buy in’ from other important organizations that provide guidance for the care of patients with HF. These include the World Heart Federation, the AHA, the ACC, the InterAmerican Society of Cardiology, the Pan-African Society of Cardiology, as well as groups representing the internal medicine and family practice communities. A useful model to consider is the iterative efforts of the universal definition of MI. Its initial version was termed a consensus document.16 With successive versions there was an expansion of the number of national societies not only simply endorsing the document but providing new reviewers (over 40 from 17 countries in a recent version), making ‘universal’ an appropriate descriptor.13 Using such criteria for defining ‘universality’ would support the next generation of clinical practice guidelines and thereby the care of patients with HF. Such improvements would then be reflected in clinical performance and quality measures.17 Future clinical trials will also benefit from such a truly universal definition of HF to refine patient eligibility criteria for trials and registries, as well as the adjudication of suspected HF events. Ultimately, convergence on a universal definition of HF will facilitate a precision medicine approach to managing this important condition. We commend the authors on their efforts and will follow with interest the subsequent evolution of this important document. Conflict of interest: E.B. reports research grant support through Brigham and Women's Hospital from: AstraZeneca, Daiichi-Sankyo, Merck, and Novartis; consulting for: Amgen, Boehringer-Ingelheim/Lilly, Cardurion, MyoKardia, NovoNordisk, and Verve. E.M.A. reports research grant through Brigham and Women's Hospital from: Daiichi-Sankyo, Eli Lilly.

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