We raised ethical concerns to proceed an invasive study despite having shown the expected results after 19 patients.

Patients with an intermediate risk (HFA-PEFF score 2-4 points) for heart failure with preserved ejection fraction (HFpEF) will be further investigated with invasive right heart catheterization. All patients with a resting pulmonary artery wedge pressure (PAWP) <15mmHg will undergo the following stress test modalities in a randomized order: (1) bicycle ergometry, (2) dynamic handgrip exercise, (3) 500ml fluid challenge over 5 minutes, (4) leg raise testing. Exercise induced HFpEF will be diagnosed if PAWP rises to >25mmHg.

Patients reporting to the investigators' clinic for in- and outpatient consultation and a HFA-PEFF score of 2-4 points will be recruited if their dyspnea is not sufficiently explained by other causes than HFpEF. Patients will undergo a baseline clinical exam, transthoracic echocardiography with measurement of diastolic parameters, and ECG. NYHA class will be reported, standard lab works (NTproBNP, GFR, CRP, Hb, PLT, blood gas analysis) will be taken. The number of patients with a PAWP increase in right heart catheterization (brachial access under sonographic guidance) from a resting value of <15mmHg to >25mmHg during stress testing will be assessed across the four interventions. During bicycle ergometry (semi-supine position) spiroergometric data and gas exchange variables (cardiopulmonary exercise testing) will be co-assessed. Between the testing modalities a 10-minute break will allow hemodynamic variables to normalize.

Inclusion Criteria:

• Age > 18 years
• Unclear etiology of dyspnea with non-invasive testing
• HFA-PEFF score 2-4 points and thus an intermediate risk for HFpEF
• Willingness to participate and obtained written consent

Exclusion Criteria:

• Consent for study participation not obtained
• Age < 18 years
• Medical contraindications to perform right heart catheterization

Patients reporting to the investigators' in- and outpatient clinic with unsolved dyspnea through non-invasive testing and a HFA-PEFF score 2-4 points and thus an intermediate risk for HFpEF. Following the diagnostic algorithm of HFpEF invasive stress testing is indicated.