Heart failure (HF) with a left ventricular ejection fraction (LVEF) >0.40 is a large medical problem, for which no drug or device has a recommendation in current HF guidelines. The prevalence of mortality and HF hospitalizations in HF with LVEF >0.40 is high, but the identification of predictors for increased risk of mortality and HF hospitalizations in this patient category remains difficult. The hypothesis of this study is that the risk of all-cause mortality and HF hospitalizations can be measured by clinical factors, imaging parameters and circulating biomarkers, and that these factors can be used in a risk profile

Objective: To assess the risk profile associated with the combined endpoint of all-cause mortality and HF hospitalizations in HF patients with LVEF >0.40.

Study design: Single-center, prospective, study.

Study population: We aim 200 patients with symptomatic heart failure (NYHA class II-III), and a recent HF hospitalization, emergency room visit or symptom relief with diuretics who have a left ventricular ejection fraction >0.40, echocardiographic evidence of left atrial enlargement or left ventricular hypertrophy, and elevated concentrations of BNP or NT-proBNP.

Study procedures: All patients will undergo echocardiography, cardiac magnetic resonance (CMR) imaging, Holter recording and blood sampling at inclusion. The 99mTc-HDP scan is optional.There is no control group.

Total follow up: Up to five years.

Main study endpoint: incidence of the combined endpoint of all-cause mortality and HF hospitalizations.

Inclusion Criteria:

Clinical criteria:

1. Age >18 years
2. Written informed consent
3. HF with moderate to severe symptoms NYHA II or III
4. Hospitalization or emergency room visit for HF or symptom relief with diuretics
5. Sinus rhythm or AF

Echocardiographic criteria:

1. LVEF >0.40
2. Left atrial size (volume ≥29 mL/m2 or LA parasternal diameter ≥45), or left ventricular hypertrophy (septal thickness or posterior wall thickness ≥11 mm) or LV diastolic dysfunction (E/e' ≥13 or mean e' septal and lateral wall <9 cm/s).

Biomarker criteria:

1. BNP >31ng/L or NT-pro-BNP>125ng/L if sinus rhythm
2. BNP >75ng/L or NT-pro-BNP>300ng/L if atrial fibrillation

Exclusion Criteria:

1. Patients unwilling or unable to sign informed consent
2. Patients with a pacemaker or ICD
3. Indication for ICD therapy according to the ESC guidelines
4. Life expectancy of less than one year
5. Significant coronary artery disease or myocardial infarction < 3 months
6. Complex congenital heart disease
7. Pregnancy

To avoid the inclusion of patients with dyspnea due to other causes, we use specific (see below) echocardiographic and biomarker criteria. From several studies is known that in patients with HF with LVEF >0.40 or AF, NT-proBNP or BNP is strongly associated with mortality an HF hospitalizations. The use of biomarker criteria will therefore help to select patients with an increased mortality risk. Therefore, by selecting HF patients with LVEF >0.40 with a previous HF hospitalization we aim to include patients at increased risk for mortality and HF hospitalizations.