The guidelines for the diagnosis and treatment of acute and chronic heart failure (HF) for 2021 are an update on the previous guidelines from 5 years previously (2016).1,2 These guidelines have been eagerly anticipated due to the need to respond with practical recommendations to the high number of scientific publications that have since been released. However, the lack of agility of these guidelines is precisely their main weakness. Thus, the document has unfortunately not considered the simultaneous publication of new evidence on the management of HF with preserved left ventricular ejection fraction (LVEF) (HFpEF). Although the guidelines are a scientific tool for improving the diagnosis and treatment of our patients, continuous updating of their recommendations is clearly required to keep them current.

The purpose of the present article is to highlight the most relevant novelties of the new guidelines and to comment on those aspects that, from a Spanish perspective, could improve understanding and local application. To do so, we address various sections of the text and include table 1 and figure 1 as summaries.

Figure 1.

Schematic representation of the main recommendations and comments and their implementation by LVEF phenotype. Green, ESC class I; yellow, ESC class IIa; orange, ESC class IIb; gray, guideline comments. ACEIs, angiotensin-converting enzyme inhibitors; ARNIs, angiotensin receptor-neprilysin inhibitors; CMRI, cardiac magnetic resonance imaging; CRT, cardiac resynchronization therapy; Fe, iron; ICD, implantable cardioverter-defibrillator; HF, heart failure; LBBB, left bundle branch block; LVEF, left ventricular ejection fraction; MR, mitral regurgitation; MRAs, mineralocorticoid receptor antagonists; mrEF, mildly reduced LVEF; NYHA, New York Heart Association functional class; pEF, preserved LVEF; PVs, pulmonary veins; rEF, reduced LVEF; SGLT2i, sodium-glucose cotransporter-2 inhibitor; SR, sinus rhythm; TTR, transthyretin.

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The new guidelines adopt the recent universal definition of HF, agreed upon by the scientific bodies of the European, North American, and Japanese cardiology societies.3 This definition continues to assign a key role to LVEF. The following aspects stand out: a) HF with reduced LVEF (HFrEF) is reestablished at LVEF ≤ 40%, vs the previous definition of < 40%, an apparently small change that may have a major impact on moving more patients toward the rEF phenotype and its treatments; b) HF with midrange LVEF is now named mildly reduced (HFmrEF) and is defined by a LVEF from 41% to 49%, another simple terminology change that moves these patients to “mild HFrEF” and closer to its treatments; c) HFpEF is maintained at LVEF ≥ 50% but, given its variability, must be interpreted in terms of the clinical context of each patient and still requires evidence of structural or functional changes, either by echocardiography or natriuretic peptides (NPs); NP elevation is included in the definition of HFpEF and removed from that of HFmrEF, although its unequivocal need is not established; in our opinion, elevated NP levels should be essential for the definition of HFpEF; d) the guidelines highlight acute HF and advanced HF as relevant entities that should be managed separately from chronic HF, given that they require distinct therapeutic approaches; e) there continues to be a discordance between the definitions based on LVEF and the cutoff points for therapeutic decisions that should be standardized; f) HF with “recovered” LVEF receives scant attention, despite being a fourth HF group in the consensus of the first universal definition of HF3; it concerns patients with HF and baseline LVEF ≤ 40% who show a ≥ 10-point increase in LVEF with a second measurement > 40%; g) the guidelines continue to recognize the usefulness of the New York Heart Association (NYHA) classification in treatment decisions, despite its limited objectivity, due to its use in the design of clinical trials; strikingly, the therapeutic recommendations are all aimed at patients in NYHA II-IV and neglect the reality of patients with HF in NYHA I; and h) a phenotype not addressed in these guidelines is that of patients with de novo HF, who deserve attention to strengthen the need to optimize the etiological study and the therapeutic approach as soon as possible after the initial diagnosis.

The algorithm is the same as before, based on signs and symptoms, NPs, and echocardiography.

The following are the 4 most relevant aspects: a) the document stresses NP measurement as a preliminary step before echocardiography to rule out the presence of HF, and the previous cutoff values remain; this places the European guidelines ahead of the North American guidelines, which do not provide reference values; b) a simplified approach is established for the diagnosis of HFpEF, based on the presence of diastolic dysfunction or elevated filling pressures (which includes elevated NPs); usefully, the various parameters are numbered (table 9 of the guidelines) and include elevated NP values specific for patients with atrial fibrillation (AF), which represents a novelty; other previously proposed diagnostic scores are not recommended; in doubtful cases, cardiopulmonary exercise testing or a diastolic stress test can be considered; a specific diagnostic algorithm would be useful for HFpEF to improve the characterization and accuracy of its diagnosis; c) recommendations on lung ultrasound must be incorporated to support the clinical diagnosis of pulmonary congestion or HF decompensation, particularly given its current rapid incorporation into clinical practice; and d) new parameters such as “myocardial deformation” and “ventricular mechanics” should be included in situations of doubt, but the guidelines do not expand on these situations.

This aspect becomes relevant in the 2021 guidelines, with the aim of individualizing specific therapeutic strategies. The most noteworthy aspects are the following: a) the genetic study of cardiomyopathies is included, with a well-formulated section and a list of mutations to be considered in our clinical practice (table 25 of the guidelines), a recommendation that poses a challenge regarding accessibility for the various professionals; b) the indications in cardiac magnetic resonance (CMR) are maintained from the previous guidelines, such as class I in cases of poor-quality echocardiography and in suspected infiltrative, inflammatory, or deposition disease; this limited recommendation does not seem in line with clinical practice and current evidence, given the usefulness of CMR in myocardial characterization and risk stratification; c) a class I recommendation is awarded to the screening of specific etiologies and comorbidities in HFpEF, a positive aspect, with special relevance for transthyretin amyloidosis; d) in the study of comorbidities, we must highlight the class I recommendation for the periodic studying of ferrokinetics, whose role in the setting of acute HF is strengthened and expanded; and e) the recommendations regarding the study of coronary heart disease are confusing, with invasive coronary angiography changed to a class IIb recommendation in intermediate-to-high–risk individuals and computed tomography coronary angiography changed to class IIa in low- or intermediate-risk individuals.

The new guidelines pay renewed attention to comorbidities and have correctly decided to separate cardiovascular and noncardiovascular comorbidities into different sections.

The following are the 4 most notable novelties related to cardiovascular comorbidities: a) after conflicting clinical trials, the document recommends percutaneous edge-to-edge repair of secondary mitral regurgitation in patients with symptomatic HFrEF to prevent hospitalization with a class IIa indication in those who meet success criteria and IIb in those who do not; notably, the criteria of the COAPT study are included for candidate selection11 but, strikingly, the surgical option continues to be favored, despite the lack of data supporting mitral valve surgery alone in these patients; b) participation in multidisciplinary teams (heart teams) and shared decision-making with patients with severe aortic stenosis and rEF: the algorithm is updated in the presence of rEF and low-gradient stenosis and the choice between valve replacement and transcatheter aortic valve implantation (TAVI) is left to shared decision-making; in this regard, a desirable inclusion would be clearer recommendation criteria that include surgical risk, as in the new guidelines on valvular heart diseases12; c) pulmonary vein isolation in patients with AF and HFrEF receives a limited IIa recommendation, in contrast to the recent guidelines on atrial fibrillation, which indicate a class I recommendation; undoubtedly, this rhythm control option should be considered at early stages but should also be individualized, given the difficulty of generalizing the approach, due to logistic reasons and the patient selection bias in the clinical trials; and d) with no novelties concerning patients with coronary heart disease, the treatment of choice continues to be coronary revascularization in symptomatic patients despite optimal medical therapy, particularly in the presence of diabetes or multivessel disease (IIa); in all patients, individualization is required, considering coronary anatomy, comorbidities, and surgical risk.

The noncardiovascular comorbidities include 4 relevant novelties: a) SGLT2i for all patients with diabetes: the abundant evidence from studies with diabetic populations has led to a class I A recommendation in all diabetic patients with high cardiovascular risk or established cardiovascular disease to prevent progression to HF; b) ferric carboxymaltose in outpatients and admitted patients with HF: determination of iron deficiency is consolidated as a fundamental part of the assessment of patients with HF (I C); while the previous guidelines recommended ferric carboxymaltose in outpatients with LVEF < 45% and iron deficiency to improve symptoms and functional capacity (IIa A), the new guidelines also recommend this treatment for admitted patients with LVEF ≤ 50% to ameliorate symptoms and reduce readmissions (IIa B), based on the outcomes of the AFFIRM trial13; c) specialized care in patients with cancer and risk of cardiotoxicity: a strong recommendation (class I) is made that at-risk patients due to their history, risk factors, or cardiotoxic agents be previously assessed by cardiologists specialized in cardio-oncology, an important recommendation that, in Spain, should be an impetus in this area, the training of professionals, and the organization of care for these patients. The document also supports with a class IIa recommendation ACEIs and beta-blockers in patients who develop ventricular dysfunction (LVEF reduction > 10 points and < 50%) during treatment; and d) there are no recommendations on renal failure despite its relevance in HF; in addition, recent favorable results obtained with SGLT2i should have allowed an indication for the prevention of HF in patients with renal failure and microalbuminuria.

The diagnostic algorithm for acute HF (AHF) is largely unchanged and the main novelty lies in treatment based on pathophysiological phenotypes together with the establishment of 3 phases: immediate, intermediate, and predischarge and early follow-up (figure 11 of the guidelines). Notable novelties in the management of AHF include: a) treatment algorithms for the 4 new phenotypes: decompensated HF, acute pulmonary edema, right HF, and cardiogenic shock (figures 7-10 of the guidelines); b) the intensive use of intravenous loop diuretics guided by urine sodium and diuresis, before the use of combinations of other diuretics (figure 13 of the guidelines); we must highlight the reference to the use of carbohydrate antigen 125 to guide diuretic treatment, based on the contributions of Spanish groups in recent years; c) the routine use of opioids is discouraged, the level of recommendation is lowered for intravenous vasodilators after neutral clinical trials (from IIa to IIb), and norepinephrine is recommended instead of adrenaline in patients with cardiogenic shock requiring vasoconstrictor support; d) the level of recommendation is increased from IIb to IIa C for mechanical circulatory support in cardiogenic shock; and e) particularly relevant are the class I recommendations regarding the predischarge need for, first, the evaluation and treatment of signs of congestion, second, the initiation and optimization of oral disease-modifying treatment (cornerstones in HFrEF), and, finally, the planning of an early revision 12 weeks after discharge.

The document recognizes the importance of the time to admission not only for resolving the acute event, but also for improving disease prognosis in the short- and long-term. However, there are no recommendations on how to organize the care transition among professionals and care levels. There is also no reference to the organization of regional care for cardiogenic shock through multidisciplinary teams and referral centers. Recent Spanish results have shown the feasibility of a shock code and improved prognosis when treatment takes place in cardiac intensive care units led by cardiologists.14

In the field of advanced HF, we must highlight the recognition of this phase of the disease with its inclusion in the main treatment algorithm and its definition with clear criteria. Taken together, the aim is to promote its organization and early referral to referral centers. Heart transplant continues to be the first option in advanced HF (I A), and the outcomes with new long-term mechanical circulatory assist devices have led to a IIa recommendation in candidates for either bridge to transplantation or destination therapy. The level of recommendation is reduced to IIb for inotrope infusion as bridge to transplantation, although no reference is made to their use as palliative care, a routine indication in Spain. In addition, the document stresses the value of the INTERMACS classification in risk stratification and decision-making.

The guidelines address various situations in this new section and highlight the circumstances or etiologies influencing diagnosis, risk stratification, and prognosis. The following aspects are notable: a) a useful algorithm is included for the management of pregnant women with HF but there is no specific section on sex differences in the disease; b) algorithms are presented for the study of myocarditis and cardiomyopathies, which include very useful criteria for diagnosis, phenotyping, and genotyping to improve characterization, a critical step toward specific treatments; c) an important therapeutic novelty, the section dedicated to amyloidosis, where treatment is recommended (class I B) for the first time with tafamidis in patients with transthyretin-mediated amyloidosis (hereditary or wild-type) in NYHA III; consequently, recommendations regarding the suspicion and diagnosis of this entity are even more important, with their underdiagnosis possibly limiting the understanding and prognosis of these patients; in this regard, multidisciplinary suspicion and diagnostic protocols are required in Spain, particularly in patients with HFmrEF or HFpEF and “warning signs”; and d) in a novel and interesting approach, atrial disease or myopathy is defined for the first time as a structural, electrophysiological, or functional change with clinical consequences, which primarily includes HFpEF and AF, an area of investigation in the coming years that should be driven by the guidelines.

The guidelines represent a direct and indirect impetus to the need for management and improved organizational care of the disease. Thus, the document clearly states that patients with HF must be managed by multidisciplinary teams that integrate patient self-care and home-based and clinic-based care programs. In addition, the recommendation for rehabilitation is the highest possible (I A) in patients who can exercise but should also be considered in those with more severe disease, frailty, or comorbidities (IIa). Moreover, the guidelines strengthen the need for organizational care built around processes such as cardiogenic shock, advanced HF, or cardio-oncology.

However, the guidelines show deficiencies in their ability to provide recommendations on how to implement this organizational need in clinical practice. These shortcomings include the following: a) the section on chronic HF monitoring is nonspecific and indicates intervals no longer than 6 months, preferably by specialists, a concept incompatible with the need for a multidisciplinary and patient-focused approach that seeks complete therapeutic optimization; b) the guidelines award the maximum recommendation to an early postdischarge follow-up but do not address the concept of transition as a specific process that also requires a multidisciplinary approach and that would support the usefulness of the early visit; c) given that the management of HF involves other specialists, such as primary care physicians and internists, it would be useful to include a proposal for interactions among specialists and levels of care, as well as continuity of care during the disease; this proposal should be initiated at diagnosis, be included in the therapeutic optimization, and be adapted to each health care area; d) the recommendation for telemedicine is IIb, based on discordant results, but does not take into account the current situation and the role that it has acquired in the post-COVID era; e) there is no reference to day hospitals as a fundamental part of the care of patients with HF and, in particular, for the outpatient resolution of decompensations; f) no specific recommendation is made regarding the role of nurses in the different phases of the disease, which is sufficiently important to warrant a specific section addressing their participation in the diagnosis, care, and treatment of patients with HF, including drug titration; we must also insist on the need for the training of nurses specialized in HF, which remains unfinished business in the Spanish health care system; and, finally, g) notably, and for the first time, a final table (table 37 of the guidelines) is included with a list of quality indicators for the care process, which should also include outcome indicators.

The new guidelines represent an organizational challenge that should allow not only the implementation of the recommendations in clinical practice, but also promote a general improvement in the management of both the overall disease and each particular patient. This would be a challenge for all and for the Spanish health care system, whose motor is undoubtedly our scientific society itself.

None.

The conflict of interest declaration documents of all authors can be seen in the supplementary data.