Background:

In patients with occult heart failure with preserved ejection fraction (HFpEF) non-invasive testing may not be diagnostic. Although exercise testing is recommended in indeterminate cases, the mode of diastolic stress testing remains unknown.

Methods:

We conducted a prospective, randomized, monocentre study (NCT04970953) investigating patients with an intermediate risk for HFpEF, determined by 2-4 points on the HFA-PEFF score and a mean pulmonary artery pressure (mPAP) < 25mmHg and pulmonary artery wedge pressure (PAWP) < 15mmHg in resting right heart catheterization (RHC). Eligibility for study inclusion was a stress-induced increase of pulmonary capillary wedge pressure (PAWP) ≥25mmHg in at least one stress test (n=19). Patients consecutively underwent the stress test modalities bicycle exercise (25W/2 minutes until maximal exertion), dynamic handgrip for one minute at 80% of the one repetition maximum , 500ml fluid challenge over 5 minutes, and 30 second passive leg raise testing in randomized order with a 10 minute resting period between each test. The primary outcome was the maximal value for PAWP in each modality during exercise (exPAWP). As secondary outcomes, modality specific differences during exercise for exmPAP, pulmonary vascular resistance (exPVR), cardiac output (exCO) as well as exmPAP/CO and exPAWP/CO were analyzed.

Results:

exPAWP was highest in exercise (31.1±3.9mmHg) testing; dynamic handgrip (18.4±6.6mmHg), leg raise (16.5±7.0mmHg), and fluid challenge (18.1±5.6mmHg) were comparable. Similarly, exmPAP (43.8±6.9mmHg vs. 28.1±7.8mmHg vs. 24.8±5.5mmHg vs. 24.4±8.2mmHg), exCO (8.4±2.5l/min vs. 7.0±2.0l/min vs. 6.0±1.2l/min vs. 6.2±1.6l/min), exmPAP/CO (2.28±2.04mmHg/l/min vs. 0.96±1.57mmHg/L/min vs. 0.93±0.91mmHg/l/min vs. 0.88±1.13mmHg/L/min), and exPAWP/CO (2.24±1.44mmHg/L/min vs. 1.01±1.39mmHg/L/min vs. 1.03±1.13mmHg/L/min vs. 1.28±0.97mmHg/L/min) were higher in bicycle testing than the other modalities. exPVR (1.4±0.7WU vs. 1.4±0.7WU vs. 1.4±0.6WU vs. 1.3±0.5WU) did not differ between modalities.

Conclusions:

We demonstrate a differential increase of PAWP depending on stress modality with the highest increase in bicycle exercise and dynamic handgrip testing. Individual cut-off values for each stress test modality have to be defined to unmask occult HFpEF with exercise right heart catheterization.