Progression From Exercise-Induced to Resting Left Atrial Hypertension in HFpEF: Impact of Reduced Atriopulmonary Compliance.

Approximately one-third of patients with heart failure with preserved ejection fraction (HFpEF) have normal pulmonary capillary wedge pressure (PCWP) at rest, with left atrial (LA) hypertension that is induced only during exercise (exercise-induced left atrial hypertension [EILAH]). EILAH may represent a discrete HFpEF phenotype or an earlier stage of HFpEF that progresses to resting left atrial hypertension (RELAH) over time. The authors investigated the clinical course of HFpEF patients with EILAH who underwent repeat invasive hemodynamic evaluation. This observational study investigated the natural history of EILAH and evaluated patients who underwent multiple invasive hemodynamic studies to assess for progression from EILAH to RELAH and then identify pathophysiological correlates of progression. Consecutively evaluated patients with HFpEF and EILAH (PCWP <15 mm Hg at rest and ≥25 mm Hg during exercise) who underwent repeat invasive hemodynamic testing were identified. Of 659 patients with EILAH, 84 underwent repeat invasive hemodynamic evaluations over a median follow-up of 1.81 years (Q1-Q3: 0.48-3.40 years). Of this group, 33 (39%) patients changed to RELAH (PCWP ≥15 mm Hg at rest) and 51 (61%) did not. Patients with a change to RELAH had a greater duration between their index and repeat catheterizations (2.68 years [Q1-Q3: 1.74-3.97 years] vs 0.99 years [Q1-Q3: 0.44-2.16 years]; P = 0.001), and they experienced greater increases in N-terminal pro-B-type natriuretic peptide (interaction P = 0.036), more severe worsening in left ventricular ejection fraction (P < 0.001), right ventricular free wall longitudinal strain (P = 0.003), and more worsening tricuspid regurgitation (+15% vs +2%; P = 0.025) compared with patients who did not transition to RELAH. Of characteristics at the index evaluation, a history of atrial fibrillation (OR: 4.57 [95% CI: 1.63-12.8]), lower LA compliance (OR: 0.47 [95% CI: 0.22-0.99]), and lower pulmonary artery compliance (OR: 0.48 [95% CI: 0.25-0.93]) were independently associated with the transition to RELAH after adjusting for follow-up duration. Many patients with HFpEF who first present with EILAH transition to RELAH, thus suggesting that EILAH may represent an earlier stage of HFpEF. A history of atrial fibrillation, impaired LA compliance, and reduced pulmonary artery compliance are associated with progression to RELAH. These findings call for further studies of interventions enhancing atriopulmonary compliance in early-stage HFpEF.