LAUSR

Background: Right heart catheterisation (RHC) using exercise-stress is the reference standard for the diagnosis of heart failure with preserved ejection fraction (HFpEF) but carries the risk of the invasive procedure. We hypothesized that real-time cardiovascular magnetic resonance (RT-CMR) exercise imaging with pathophysiologic data at excellent temporal and spatial resolution may represent a contemporary non-invasive alternative for diagnosing HFpEF. Methods: The HFpEF stress trial (DZHK-17, NCT03260621) prospectively recruited 75 patients with echocardiographic signs of diastolic dysfunction and dyspnea on exertion (E/e'>8, New York Heart Association (NYHA) class ≥II) to undergo echocardiography, RHC and RT-CMR at rest and during exercise-stress. HFpEF was defined according to pulmonary capillary wedge pressure (PCWP ≥15mmHg at rest or ≥25mmHg during exercise stress). RT-CMR functional assessments included time-volume curves for total and early (1/3) diastolic left ventricular (LV) filling, left atrial (LA) emptying and LV/LA long axis strain (LAS). Results: HFpEF patients (n=34, median PCWP rest 13mmHg, stress 27mmHg) had higher E/e' (12.5 vs. 9.15), NT-proBNP (255 vs. 75ng/l) and LA volume index (43.8 vs. 36.2ml/m2) compared to non-cardiac dyspnea patients (n=34, rest 8mmHg, stress 18mmHg, p≤0.001 for all). Seven patients were excluded due to the presence of non HFpEF cardiac disease causing dyspnea on imaging. There were no differences in RT-CMR LV total and early diastolic filling at rest and during exercise-stress (p≥0.164) between HFpEF and non-cardiac dyspnea. RT-CMR revealed significantly impaired LA total and early (p<0.001) diastolic emptying in HFpEF during exercise-stress. RT-CMR exercise-stress LA LAS was independently associated with HFpEF (adjusted odds ratio 0.657, 95% confidence interval [0.516; 0.838], p=0.001) after adjustment for clinical and imaging parameters and emerged as the best predictor for HFpEF (area under the curve rest 0.82 vs. exercise-stress 0.93, p=0.029). Conclusions: RT-CMR allows highly accurate identification of HFpEF during physiological exercise and qualifies as a suitable non-invasive diagnostic alternative. These results will need to be confirmed in multi-centre prospective research studies to establish widespread routine clinical use. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique Identifier: NCT03260621.