. 2023 Jun 29;10:1194693. doi: 10.3389/fcvm.2023.1194693

Table 1.

Inclusion and exclusion criteria for the PRIORITY trial.

HFpEF stage	Inclusion criteria	Exclusion criteria
A “at risk”	History of treated or untreated hypertension (blood pressure 130/90–159/99 mmHg) AND/OR Prediabetes with either: • Fasting plasma glucose: 100–125 mg/dl (5.6–6.9 mmol/L) • HbA1c: 5.7%–6.4% • HOMA-IR >2.0 AND/OR Obesity: 30 kg/m² ≥ BMI ≤ 42 kg/m² AND/OR • Diabetes treated with anti-diabetics	• Significant illness during the last 6 weeks • Known severe arrhythmia (i.e., the occurrence of complex ventricular arrhythmia or other arrhythmia, including second- or third degree AV block, that interferes with normal maintenance of cardiac output during exercise and with functional or prognostic significance) • Significant myocardial ischemia (defined as marked ST displacement (horizontal or downsloping of >2 mm, measured 60–80 ms after the J point at the end of the QRS complex) or increasing chest pain, hemodynamic deterioration, or exercise-induced arrhythmia at baseline testing • Co-morbidity that may significantly negatively influence 1-year prognosis (e.g., oncological diseases, auto-immune disorders, etc.) • Non-cardiac causes for heart failure-like symptoms ◦ Severe chronic obstructive pulmonary disease (FEV1 <50%) ◦ NYHA class IV ◦ Significant peripheral artery disease (Fontaine > IIb) ◦ Specific cardiomyopathy (e.g., amyloidosis, congenital heart disease) ◦ Chronic kidney disease (eGFR < 30 ml/min) or on dialysis • Participation in another clinical intervention trial • Any inability or contraindication to perform a cardiopulmonary exercise test or to participate in an exercise program (physiological, physical, or mental) as considered by the supervising physician (KG, GC, EVC) • Inability to fill in questionnaires presented in Dutch. • Advanced HF (stage D)
B “pre-HFpEF”	CV risk factors as mentioned under stage A AND Subclinical signs of left ventricular diastolic dysfunction and/or raised left ventricular filling pressures (see Table 2.)
C “symptomatic HF”	Criteria as mentioned under stage B with either: • Heart failure hospitalisation AND/OR • Treatment with diuretics AND/OR • Symptoms and/or signs compatible with a diagnosis of heart failure with an HFA-PEFF total score of ≥5

HFpEF stage

Inclusion criteria

Exclusion criteria

A “at risk”

History of treated or untreated hypertension (blood pressure 130/90–159/99 mmHg) AND/OR Prediabetes with either:

•
Fasting plasma glucose: 100–125 mg/dl (5.6–6.9 mmol/L)
•
HbA1c: 5.7%–6.4%
•
HOMA-IR >2.0

AND/OR Obesity: 30 kg/m² ≥ BMI ≤ 42 kg/m² AND/OR

•
Diabetes treated with anti-diabetics

•
Significant illness during the last 6 weeks
•
Known severe arrhythmia (i.e., the occurrence of complex ventricular arrhythmia or other arrhythmia, including second- or third degree AV block, that interferes with normal maintenance of cardiac output during exercise and with functional or prognostic significance)
•
Significant myocardial ischemia (defined as marked ST displacement (horizontal or downsloping of >2 mm, measured 60–80 ms after the J point at the end of the QRS complex) or increasing chest pain, hemodynamic deterioration, or exercise-induced arrhythmia at baseline testing
•
Co-morbidity that may significantly negatively influence 1-year prognosis (e.g., oncological diseases, auto-immune disorders, etc.)
•
Non-cardiac causes for heart failure-like symptoms
- ◦
  Severe chronic obstructive pulmonary disease (FEV1 <50%)
- ◦
  NYHA class IV
- ◦
  Significant peripheral artery disease (Fontaine > IIb)
- ◦
  Specific cardiomyopathy (e.g., amyloidosis, congenital heart disease)
- ◦
  Chronic kidney disease (eGFR < 30 ml/min) or on dialysis
•
Participation in another clinical intervention trial
•
Any inability or contraindication to perform a cardiopulmonary exercise test or to participate in an exercise program (physiological, physical, or mental) as considered by the supervising physician (KG, GC, EVC)
•
Inability to fill in questionnaires presented in Dutch.
•
Advanced HF (stage D)

B “pre-HFpEF”

CV risk factors as mentioned under stage A AND Subclinical signs of left ventricular diastolic dysfunction and/or raised left ventricular filling pressures (see Table 2.)

C “symptomatic HF”

Criteria as mentioned under stage B with either:

•
Heart failure hospitalisation

AND/OR

•
Treatment with diuretics

AND/OR

•
Symptoms and/or signs compatible with a diagnosis of heart failure with an HFA-PEFF total score of ≥5

HbA1c, hemoglobin A1c; HOMA-IR, homeostatic model assessment of insulin resistance; BMI, body mass index; CV, cardiovascular; HFA-PEFF, heart failure association—pretest assessment, echocardiographic and natriuretic peptide score, functional testing in case of uncertainty, final etiology.