Authors: Mary Norine Walsh, Lars Kober, Karen Sliwa, Marianna Adamo, Anubha Agarwal, Amitava Banerjee, Biykem Bozkurt, … Show All …
Abstract
Heart failure (HF) remains a pressing health concern, with rising prevalence globally. Subjectivity and ambiguity in the definition of HF and its antecedent stages have limited research, global surveillance, and prevention programs. To address this, several cardiac societies and foundations convened to standardize the definition of HF in 2021 and designated stage B or pre-HF to identify individuals at risk of developing HF. In subsequent years, substantial progress and changes have been made in aspects of preventing HF, improving HF diagnosis and management, and recognizing the importance of the affected individual’s voice. Global differences and disparities in HF are better understood, as are causes and comorbidities leading to differences in care, which are also influenced by access to care. This consensus document presents the Second Universal Definition of Heart Failure, aiming to standardize terminology and facilitate a uniform approach for clinicians, researchers, health systems, and policymakers. In this definition, the classification of HF phenotypes moves away from rigid left ventricular ejection fraction cutoffs, instead grouping HF into reduced, preserved, and improved ejection fraction categories to better reflect clinical realities. A universal classification of HF causes is also proposed. The document also addresses the dynamic trajectories of HF—improvement, remission, and recovery—and highlights the impact of social determinants and geographic variation on HF risk and outcomes. By providing a comprehensive, standardized framework for HF definition and classification, this document seeks to improve prevention, early detection, and management of HF worldwide, ultimately enhancing patient care and advancing global cardiovascular health.
Universal definitions of clinical syndromes have been instrumental in guiding diagnosis by describing a combination of symptoms, biomarkers, imaging studies, and pathology that clearly characterize the syndrome. The first Universal Definition and Classification of Heart Failure1 clarified definitions of heart failure (HF) that had previously been ambiguous, poorly understood, and lacking in standardization.
Since then, the incidence and prevalence of HF, particularly among individuals with preserved ejection fraction (HFpEF), have continued to increase, as has the risk of HF hospitalization and mortality.2,3 The growing prevalence of HF is driven by the increasing numbers of individuals with HFpEF, the aging of the population, and secular trends in the prevalence of comorbidities that drive HF risk. In addition, advances in technology and the development of more advanced imaging methods (magnetic resonance imaging, positron emission tomography), allowing earlier and more accurate disease detection, along with improvements in survival resulting from the availability of expanded treatment options, have increased prevalence. Improved strategies for early diagnosis of HF leveraging artificial intelligence may enhance HF detection even further over traditional biomarker- and imaging-based approaches, making estimates of the total population-level HF burden more accurate.
Definitions of HF, including participant inclusion criteria, vary widely in HF clinical trials. Specifically, requirements for inclusion of only narrow ranges of left ventricular ejection fraction (LVEF) often obscure possible benefits of therapies for HF phenotypes that range outside that criterion.4
The identification of more diverse phenotypes of HF is rapidly expanding as a result of improvements in and greater availability of advanced imaging technologies. Routine genetic screening—as ease of testing has increased and cost has decreased—has brought new understanding of genetic and familial cardiomyopathies to the clinic and to many more patients and families. In addition, the impact of comorbid diseases and their therapies on HF phenotypes has made the accurate identification of such phenotypes crucial to aid in appropriate and effective therapies. The development and greater availability of HF treatments that are specific to HF phenotype drive the necessity for accurate identification and diagnosis.
Disparities in HF care are present worldwide, with access to diagnosis and quality treatment being influenced by race, ethnicity, sex, income, geography, access to and coverage of health care, and socioeconomic status.5 These disparities in care are particularly concerning for high-risk, underserved groups, who have the highest risk for HF hospitalization and death.6,7
These considerations underscore the need for the current update. As with other universal definitions such as that of myocardial infarction,8 the impetus for this updated document is to address changes in disease manifestations, diagnostic strategies, and understanding of pathophysiology. The current document serves as an update of the first definition1 with collaboration by the American College of Cardiology, the American Heart Association, the European Society of Cardiology, and the World Heart Federation. This document is not a clinical practice guideline, nor is it a clinical decision support document. Treatment recommendations will remain reserved for the current and future professional society HF guidelines documents.9,10
Proposed Changes in the Definition: Classification, Phenotypes, and Trajectories
Definition of HF Syndrome
As outlined in the first Universal Definition of Heart Failure,1 HF is a clinical syndrome with diverse causes characterized by the presence of typical symptoms, physical examination signs, and laboratory or imaging abnormalities suggestive of pulmonary or systemic congestion or changes in cardiac output that can be attributed to an underlying structural or functional cardiac abnormality. Clinical symptoms and signs of HF include dyspnea on exertion, orthopnea, jugular venous distention, rales, S3 gallop, and abdominal and leg swelling. Diagnostic certainty is amplified by confirmatory elevation in natriuretic peptide (BNP [B-type natriuretic peptide] or NT-BNP [N-terminal B-type natriuretic peptide]) levels or imaging evidence (lung ultrasound, chest radiography, echocardiography, computed tomography) of pulmonary congestion and elevated intracardiac filling pressures. It is important to note that HF is defined by the accumulation of suggestive features in a comprehensive assessment rather than by a single diagnostic test. As an example, a substantial proportion of individuals with HFpEF have normal natriuretic peptide levels despite unequivocal invasive hemodynamic evidence of HF, for example, elevation of ventricular filling pressure at rest or exercise.11,12 When HF is suspected, imaging is important to evaluate for structural or functional cardiac abnormalities that may inform the cause of HF and help guide the approach to treatment.
Permanence of the Diagnosis/Condition
As outlined in the first Universal Definition of Heart Failure,1 HF progresses in stages from those at risk (stage A) to those with structural heart disease (pre-HF or stage B), those with symptomatic HF (stage C), and those with advanced disease (stage D). Once a diagnosis of symptomatic HF is established, individuals with HF are generally considered to have the diagnosis permanently, even if the clinical condition improves with treatment.
For the purpose of selecting medical treatment, individuals with HF are commonly segregated by LVEF into those with preserved or mildly reduced ejection fraction (EF) and those with reduced EF. There are limitations to phenotype categorization by EF alone (or by specific cutoff values for EF), and there is evolving evidence for the efficacy and safety of therapies across different EF ranges. Acknowledging that EF may change with effective HF treatment, current guidelines recognize a separate subgroup of individuals whose EF increases with time and medical intervention as a separate category of HF with “improved” EF, emphasizing that these individuals may still be at risk for HF events. Although contention remains about the precise numeric thresholds of EF that should be used for HF phenotyping,13 it is essential to recognize the clinical relevance of incorporating the individual’s trajectory in determining the optimal approach to guideline-directed medical therapy and prognosis.
Definition and Criteria for Stages of HF
The first Universal Definition and Classification of Heart Failure1 reviewed the American Heart Association/American College of Cardiology staging system10 and renamed stage B as pre-HF, emphasizing early detection, close monitoring, and proactive management to prevent symptomatic HF.10,14 This consensus reaffirms the first Universal Definition and Classification of Heart Failure staging system, as shown in Table 1.
