Prognostic impact of Framingham heart failure criteria in heart failure with preserved ejection fraction

Abstract

Aims: This study aims to assess prognostic impact of Framingham criteria for heart failure (FC-HF) in patients with stable heart failure (HF) with preserved ejection fraction (HFpEF).

Methods and results: In the prospective Karolinska-Rennes (KaRen) study, we assessed stable HFpEF patients after an acute HF episode. We evaluated associations between the four descriptive models of HFpEF and the composite endpoint of all-cause mortality and HF hospitalization. The descriptive models were FC-HF alone, FC-HF + natriuretic peptides (NPs) according to the PARAGON trial, FC-HF + NPs + echocardiographic HFpEF criteria according to European Society of Cardiology HF guidelines, and FC-HF + NPs + echocardiographic criteria according to the PARAGON trial. Out of the 539 patients enrolled in KaRen, 438 returned for the stable state revisit after 4-8 weeks, 13 (2.4%) patients died before the planned follow-up, and 88 patients (16%) declined or were unable to return. Three hundred ninety-nine patients have FC registered at follow-up, and among these, the four descriptive models were met in 107 (27%), 82 (22%), 61 (21%), and 69 (22%) patients, and not met in 292 (73%). The 107 patients that had FC-HF at stable state (descriptive model 1) could also be part of the other models because all patients in models 1-4 had to fulfil the FC-HF. The patients in model 0 did not fulfil the criteria for FC-HF but could have single FC. Of single FC, only pleural effusion predicted the endpoint [hazard ratio (HR) 3.38, 95% confidence interval (CI) 1.47-7.76, P = 0.004]. Patients without FC-HF had better prognosis than patients meeting FC-HF. The unadjusted associations between the four HFpEF descriptive models and the endpoint were HR 1.54, 95% CI 1.14-2.09, P = 0.005; HR 1.71, 95% CI 1.24-2.36, P = 0.002; HR 1.95, 95% CI 1.36-2.81, P = 0.001; and HR 2.05, 95% CI 1.45-2.91, P < 0.001, for descriptive models 1-4, respectively. No descriptive model independently predicted the endpoint.

Conclusions: In ambulatory HFpEF patients, a quarter met FC-HF, while most met NP and echocardiography criteria for HF. Residual FC-HF tended to be associated with increased risk for mortality and HF hospitalization, further strengthened by NPs and echocardiographic criteria, highlighting its role in clinical risk assessment.

Keywords: Echocardiography; Framingham criteria; Heart failure with preserved ejection fraction; Natriuretic peptides; Prognosis.

Conflict of interest statement

In this study, the authors had full access to all the data and take responsibility for its integrity and the data analysis. There are no conflicts of interest related to this study. However, to the extent of the findings in the KaRen trial that may affect the use of heart failure drugs or devices and future trials, we disclose the following: G.S.: research grants from Boehringer Ingelheim and Merck Sharp & Dohme; honoraria from Vifor, Servier, AstraZeneca, and Roche; C.H.: consulting fees from Novartis and speaker and honoraria from MSD; E.D.: speaker honoraria and consulting fees from Novartis, AstraZeneca; J.C.D.: research grants, speaker honoraria, and consulting fees from Medtronic and St Jude Medical; L.H.L.: research grants and speaker and honoraria from AstraZeneca, consulting honoraria from Novartis and St Jude Medical, and research grants from Boston Scientific; C.L.: principal investigator of REVERSE, a CRT study sponsored by Medtronic research grants, speaker honoraria, and consulting fees from Medtronic, speaker honoraria and consulting fees from St. Jude Medical.

© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Figures

Figure 1

Flowchart of patients showing their distribution to descriptive models 1–4 of heart failure (HF) with preserved ejection fraction and those no longer fulfilling inclusion criteria for the study at stable state [absence of Framingham criteria for HF (FC‐HF), descriptive model 0]. For example, 69/107 patients with FC‐HF fulfilled criteria for descriptive model 4. FC‐HF: two major or one major + two minor. Natriuretic peptide (NP) criteria PARAGON (NP‐P): NT‐proBNP in sinus rhythm >300; in atrial fibrillation >900; BNP in sinus rhythm >100; and in atrial fibrillation >400. European Society of Cardiology ECHO HF with preserved ejection fraction criteria (ECHO‐ESC): relevant structural heart disease [left atrial (LA) enlargement/left ventricular (LV) hypertrophy] and/or diastolic dysfunction. Structural heart disease: increased LA volume index (>34 mL/m2) and/or increased LV mass index >95 g/m2 in women and >115 g/m2 in men. Diastolic dysfunction: reduced é (é average <9 cm/s) and/or increased E/é ratio (>13). PARAGON ECHO structural heart disease criteria (ECHO‐P): at least one of the following: LA volume index >28 mL/m2 and/or LA diameter >38 mm. LV hypertrophy: interventricular septal thickness >10 mm and/or posterior wall thickness in diastole >10 mm.

Figure 2

Prevalence of individual Framingham criteria for heart failure at stable state according to the four descriptive models of heart failure with preserved ejection fraction clarified in the methods section.

Figure 3

Kaplan–Meier (KM) curves showing the primary endpoint (survival free from heart failure hospitalization) for the four descriptive models (DMs) of heart failure with preserved ejection fraction clarified in the methods section. All definitions compared with descriptive model 0 (patients without heart failure according to Framingham criteria), P‐values from unadjusted cox regression analyses. ESC, European Society of Cardiology; FC‐HF, Framingham criteria for heart failure; NP, natriuretic peptide.

Figure 4

Heart failure with preserved ejection fraction according to the four descriptive models, clarified in the Methods section, as predictors of all‐cause mortality/heart failure hospitalization compared with descriptive model 0 (patients without heart failure according to Framingham criteria). Adjustments for gender, age, glomerular filtration rate, log haemoglobin, log sodium, systolic blood pressure, atrial fibrillation, coronary artery disease, chronic obstructive pulmonary disease, type 2 diabetes mellitus, cancer, and New York Heart Association class. CI, confidence interval; HR, hazard ratio.