Risk Prediction Models and Novel Prognostic Factors for Heart Failure with Preserved Ejection Fraction: A Systematic and Comprehensive Review

Abstract

Background: Patients with heart failure with preserved ejection fraction (HFpEF) have large individual differences, unclear risk stratification, and imperfect treatment plans. Risk prediction models are helpful for the dynamic assessment of patients' prognostic risk and early intensive therapy of high-risk patients. The purpose of this study is to systematically summarize the existing risk prediction models and novel prognostic factors for HFpEF, to provide a reference for the construction of convenient and efficient HFpEF risk prediction models.

Methods: Studies on risk prediction models and prognostic factors for HFpEF were systematically searched in relevant databases including PubMed and Embase. The retrieval time was from inception to February 1, 2023. The Quality in Prognosis Studies (QUIPS) tool was used to assess the risk of bias in included studies. The predictive value of risk prediction models for end outcomes was evaluated by sensitivity, specificity, the area under the curve, C-statistic, C-index, etc. In the literature screening process, potential novel prognostic factors with high value were explored.

Results: A total of 21 eligible HFpEF risk prediction models and 22 relevant studies were included. Except for 2 studies with a high risk of bias and 2 studies with a moderate risk of bias, other studies that proposed risk prediction models had a low risk of bias overall. Potential novel prognostic factors for HFpEF were classified and described in terms of demographic characteristics (age, sex, and race), lifestyle (physical activity, body mass index, weight change, and smoking history), laboratory tests (biomarkers), physical inspection (blood pressure, electrocardiogram, imaging examination), and comorbidities.

Conclusion: It is of great significance to explore the potential novel prognostic factors of HFpEF and build a more convenient and efficient risk prediction model for improving the overall prognosis of patients. This review can provide a substantial reference for further research.

Keywords: Heart failure with preserved ejection fraction; biomarkers; dynamic assessment; prognostic factor; risk prediction model; risk stratification.

Fig. (1)

PRISMA flowchart of the literature screening process.

Fig. (2)

Combination of existing HFpEF risk prediction models and potential novel prognostic factors.Abbreviations: HFpEF, heart failure with preserved ejection fraction; BMI, body mass index; BNP, B-type natriuretic peptide; NT-proBNP, N-terminal pro B-type natriuretic peptide; WBC, white blood cell; CRP, C-reactive protein; BUN, blood urea nitrogen; SBP, systolic blood pressure; DBP, diastolic blood pressure; ECG, electrocardiogram; LVEF, left ventricular ejection fraction; E/e’, the ratio of peak mitral valve blood flow velocity in early diastole to peak mitral valve annulus velocity in early diastole; PASP, pulmonary artery systolic pressure; IVCD, inferior vena cava diameter; LVEED, left ventricle end-diastolic diameter; LVOT VTI, left ventricle outflow tract velocity-time integral; RV, right ventricular; RVEF, right ventricular ejection fraction; TR, tricuspid regurgitation; GLS, global longitudinal strain; LAVI, left atrial volume index; LVMI, left ventricular mass index; LVWT, left ventricular wall thickness; RWT, relative wall thickness; NYHA, New York Heart Association; HF, heart failure; AF, atrial fibrillation; MI, myocardial infarction; DM, diabetes mellitus; COPD, chronic obstructive pulmonary disease; ACEI, angiotensin-converting enzyme inhibitor; HFH, heart failure hospitalization; CVH, cardiovascular hospitalization; ACM, all-cause mortality; CCE, cardiovascular and cerebrovascular event; RH, rehospitalization; CVE, cardiovascular events; SCD, sudden cardiac death; CVD, cardiovascular death; CD, cardiac death; HFR, heart failure rehospitalization; PFD, pump failure death; ACA, aborted cardiac arrest; LTPA, leisure-time physical activity; GDF-15, growth differentiation factor-15; Gal-3, galectin 3; sST2, soluble suppression of tumorigenesis-2; cBIN1, cardiac bridging integrator 1; vWF, von Willebrand factor; NRP, neuropilin; OPN, osteopontin; DHA, docosahexaenoic acid; FABP4, fatty acid-binding protein 4; TMAO, trimethylamine N-oxide; cTnI, cardiac troponin I; hs-cTnI, high-sensitivity cardiac troponin I; CA125, carbohydrate antigen 125; cumBP, time-averaged cumulative blood pressure; PP, pulse pressure; T_p-T_e interval, T wave peak-T wave end interval; LAV_max, maximum left atrial volume; LAV_min, minimum left atrial volume; LVGLS, left ventricular global longitudinal strain; RVSBP, right ventricular systolic blood pressure; EAT, epicardial adipose tissue.