New strategies and therapies for the prevention of heart failure in high‐risk patients

Abstract

Despite declines in total cardiovascular mortality rates in the United States, heart failure (HF) mortality rates as well as hospitalizations and readmissions have increased in the past decade. Increases have been relatively higher among young and middle‐aged adults (<65 years). Therefore, identification of individuals HF at‐risk (Stage A) or with pre‐HF (Stage B) before the onset of overt clinical signs and symptoms (Stage C) is urgently needed. Multivariate risk models (e.g., Pooled Cohort Equations to Prevent Heart Failure [PCP‐HF]) have been externally validated in diverse populations and endorsed by the 2022 HF Guidelines to apply a risk‐based framework for the prevention of HF. However, traditional risk factors included in the PCP‐HF model only account for half of an individual's lifetime risk of HF; novel risk factors (e.g., adverse pregnancy outcomes, impaired lung health, COVID‐19) are emerging as important risk‐enhancing factors that need to be accounted for in personalized approaches to prevention. In addition to determining the role of novel risk‐enhancing factors, integration of social determinants of health (SDoH) in identifying and addressing HF risk is needed to transform the current clinical paradigm for the prevention of HF. Comprehensive strategies to prevent the progression of HF must incorporate pharmacotherapies (e.g., sodium glucose co‐transporter‐2 inhibitors that have also been termed the “statins” of HF prevention), intensive blood pressure lowering, and heart‐healthy behaviors. Future directions include investigation of novel prediction models leveraging machine learning, integration of risk‐enhancing factors and SDoH, and equitable approaches to interventions for risk‐based prevention of HF.

Scalable Risk Stratification for Heart Failure Using Artificial Intelligence applied to 12-lead Electrocardiographic Images: A Multinational Study

“…The ability to identify individuals at the highest risk for HF is crucial given the high clinical and economic impact of HF, along with the availability of evidencebased risk-mitigating therapies. [6][7][8][9] Thus, there has been substantial investigation into defining risk for HF. [12][13][14][15][16][17][18] Notably, blood-based biomarkers have been a key focus on investigation, with an NT-proBNP of 125pg/ml associated with 2.4-fold higher risk of incident HF.…”

“…3–5 Identifying individuals most likely to develop future HF can alleviate these risks with early initiation of low-cost medical therapies that have been proven in clinical practice guidelines to modify the trajectory of the disease, reducing both the risk for incident clinical HF and improving life expectancy. 6–9…”

“…[3][4][5] Identifying individuals most likely to develop future HF can alleviate these risks with early initiation of low-cost medical therapies that have been proven in clinical practice guidelines to modify the trajectory of the disease, reducing both the risk for incident clinical HF and improving life expectancy. [6][7][8][9] Several serum assay-and clinical score-based strategies have been proposed to predict incident HF. [10][11][12][13][14][15][16][17][18] While serum assay-based biomarkers such as N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-Tn) are independently associated with an elevated risk of incident HF, 19,20 they are limited by the need for an invasive blood draw and frequent inaccessibility at the point-of-care.…”

Prediction models for heart failure in the community: A systematic review and meta‐analysis

“…Whilst there have been advances in the treatment of stage C HF across the ejection fraction spectrum, prognosis still remains poor, 3 emphasizing the need to shift upstream to prevent irreversible myocardial damage that heralds symptomatic HF 49 . The 2022 AHA/ACC/HFSA HF guidelines recommend estimation of risk of incident HF in the general population, 5 and specifically example the Framingham Heart Failure risk score, 50 Health ABC Heart Failure score, 51 ARIC risk score, 41 and PCP‐HF 33 .…”

“…Whilst there have been advances in the treatment of stage C HF across the ejection fraction spectrum, prognosis still remains poor, 3 emphasizing the need to shift upstream to prevent irreversible myocardial damage that heralds symptomatic HF. 49 The 2022 AHA/ACC/HFSA HF guidelines recommend estimation of risk of incident HF in the general population, 5 and specifically example the Framingham Heart Failure risk score, 50 Health ABC Heart Failure score, 51 ARIC risk score, 41 and PCP-HF. 33 The Framingham Heart Failure risk score and Health ABC Heart Failure score were not included in this study as they require ECG interpretation for left ventricular hypertrophy, but ECGs are missing in over three-quarters of routinely-collected community-based medical records.…”