Prognostic and diagnostic implications of impaired rest and exercise-stress left atrial compliance in heart failure with preserved ejection fraction: Insights from the HFpEF stress trial.

BACKGROUND: With emerging therapies, early diagnosis of heart failure with preserved ejection fraction (HFpEF) comes to the fore. Whilst the reference standard of exercise-stress right heart catheterisation is well established, the clinical routine struggles between feasibility of exercise-stress and diagnostic accuracy of available tests. METHODS: The HFpEF Stress Trial (DZHK-17) prospectively enrolled 75 patients with exertional dyspnoea and echocardiographic signs of diastolic dysfunction (E/e' > 8) who underwent simultaneous rest and exercise-stress echocardiography and right heart catheterisation (RHC). HFpEF was defined according to pulmonary capillary wedge pressure (HFpEF: PCWP rest: ≥15 mmHg stress: ≥25 mmHg). Patients were classified as non-cardiac dyspnoea (NCD) in the absence of HFpEF and cardiovascular disease. LA compliance was defined as reservoir strain (Es)/(E/e'). Follow-up was conducted after 4 years to evaluate cardiovascular hospitalisation (CVH). RESULTS: The final study population included 68 patients (HFpEF n = 34 and NCD n = 34) of which 23 reached the clinical endpoint, 1 patient was lost to follow-up. Patients with HFpEF according to the HFA-PEFF score (≥5 points) had significantly lower LA compliance at rest (p < 0.001) compared to patients with a score ≤ 4. LA compliance at rest outperformed E/e' (AUC 0.78 vs 0.87, p = 0.024) and showed a statistical trend to outperform Es (AUC 0.79 vs 0.87, p = 0.090) for the diagnosis of HFpEF. LA compliance at rest predicted CVH (HR 2.83, 95% CI 1.70-4.74, p < 0.001) irrespective of concomitant atrial fibrillation. CONCLUSIONS: LA compliance at rest can be obtained from clinical routine imaging and bears strong diagnostic and prognostic accuracy. Addition of LA compliance can improve the role of echocardiography as the primary test and gatekeeper.

Real-time cardiovascular magnetic resonance imaging for non-invasive characterisation of heart failure with preserved ejection fraction: final outcomes of the HFpEF stress trial.

BACKGROUND: The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. Recently, the HFpEF Stress Trial demonstrated feasibility and accuracy of non-invasive cardiovascular magnetic resonance (CMR) real-time (RT) exercise-stress atrial function imaging for early identification of HFpEF. However, no outcome data have yet been presented. METHODS: The HFpEF Stress Trial (DZHK-17) prospectively recruited 75 patients with dyspnea on exertion and echocardiographic preserved EF and signs of diastolic dysfunction (E/e' > 8). 68 patients entered the final study cohort and were characterized as HFpEF (n = 34) or non-cardiac dyspnea (n = 34) according to pulmonary capillary wedge pressure (HFpEF: PCWP rest: ≥ 15 mmHg stress: ≥ 25 mmHg). These patients were contacted by telephone and hospital charts were reviewed. The clinical endpoint was cardiovascular events (CVE). RESULTS: Follow-up was performed after 48 months; 1 patient was lost to follow-up. HFpEF patients were more frequently compared to non-cardiac dyspnea (15 vs. 8, p = 0.059). Hospitalised patients during follow-up had higher H2FPEF scores (5 vs. 3, p < 0.001), and impaired left atrial (LA) function at rest (p ≤ 0.002) and stress (p ≤ 0.006). Impairment of CMR-derived atrial function parameters at rest and during exercise-stress (p ≤ 0.003) was associated with increased likelihood for CVE. CMR-Feature Tracking LA Es/Ee (p = 0.016/0.017) and RT-CMR derived LA long axis strain (p = 0.003) were predictors of CVE independent of the presence of atrial fibrillation. CONCLUSIONS: Left atrial function emerged as the strongest predictor for 4-year outcome in the HFpEF Stress Trial. A combination of rest and exercise-stress LA function quantification allows accurate diagnostic and prognostic stratification in HFpEF. CLINICALTRIALS: gov: NCT03260621.