Active left atrial ejection fraction as a non-invasive marker in pulmonary hypertension secondary to heart failure

Patients with pulmonary hypertension (PH) secondary to left heart failure (HF) exhibit a complex pathophysiological profile and poor prognosis. Left atrial (LA) function is pivotal in the progression of this disease, yet its predictive significance remains exclusive. This study aimed to explore the predictive capability of LA metrics in this population and compare them with other common predictors. In this retrospective study, consecutive patients with PH secondary to HF who underwent cardiac magnetic resonance (CMR) imaging between December 2010 and December 2021 were enrolled. The composite endpoint was defined as all-cause death, heart-lung transplantation, or left ventricular assist device implantation. Survival analyses were performed using Kaplan-Meier curves and Cox regression analyses. A total of 174 patients with PH secondary to HF, with a mean age of 53.2 ± 14.9 years, including 90 men, were included in the final analysis. During a median follow-up of 31.9 months, 33.3% (58/174) of the patients with PH reached the endpoints. There was a fair correlation between active left atrial ejection fraction (LAEF) and pulmonary artery wedge pressure (r = −0.397, p = 0.044). Active LAEF had a strong correlation with oxygen consumption at anaerobic threshold (r = 0.769, p < 0.001) and peak oxygen consumption (r = 0.754, p < 0.001). Active LAEF demonstrated comparable prognostic performance to other variables measured by echocardiography or CMR. After adjusting for clinical variables and left ventricular ejection fraction, active LAEF was still an independent predictor for adverse events (C-statistic: 0.784). Subgroup analysis among HF patients with preserved ejection fraction demonstrated that those with active LAEF ≤8.6% had a 7.05-fold higher risk of experiencing the composite endpoint compared to those with active LAEF >8.6%. Although active LAEF does not demonstrate statistical improvement in outcome discrimination compared to established metrics, it may still merit consideration for assessing disease severity and prognosis in patients with PH secondary to HF. The integration of active LAEF and HF subtypes may stratify individuals at different levels of risk. In the first row, the left MR image showed representative indexed left atrial volume-time phases curves in patients with (blue line) and without (orange line) active LAEF ≤8.6% (5.1% vs 21.8%), of whom presented comparable total LAEF (21.3% vs 23.7%) and LVEF (57.3% vs 58.3%). The right MR image showed representative RVGLS-time phase curves in patients with (blue line) and without (orange line) RVGLS ≥−17.5% (−15.4% vs −28.9%), of whom presented comparable left ventricular ejection fraction (59.6% vs 57.3%). In the second row, scatterplots show correlations between exercise capacity and active LAEF. The dotted lines represented the 95% prediction intervals. Although not statistically significant, cases with active LAEF ≤8.6% were more likely to have higher mean, systolic, and diastolic PAP and PAWP. Active LAEF exhibited a reasonable performance for predicting composite endpoints, with area under the curves of 0.74, 0.74, 0.74, and 0.73 for predicting 1-, 3-, 5-, and 9-year events rates, respectively. In multivariable Cox analyses, after adjusting for systolic blood pressure, risk stratification integrated by the subtype of heart failure and active LAEF was an independent predictor of adverse events in PH patients secondary to heart failure. MR magnetic resonance, LAEF left atrial ejection fraction, RVGLS right ventricular global longitudinal strain, VO 2 AT oxygen consumption at anaerobic threshold, PAP pulmonary arterial pressure, PAWP pulmonary artery wedge pressure, HFpEF heart failure with preserved ejection fraction, HFrEF heart failure with reduced ejection fraction, HFmrEF heart failure with mildly reduced ejection fraction