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Exercise-Induced Left Atrial Hypertension in Heart Failure With Preserved Ejection Fraction. 2023
Sheldon E Litwin, and
Jan Komtebedde, and
Mo Hu, and
Daniel Burkhoff, and
Gerd Hasenfuß, and
Barry A Borlaug, and
Scott D Solomon, and
Michael R Zile, and
Rajeev C Mohan, and
Rami Khawash, and
Aaron L Sverdlov, and
Peter Fail, and
Eugene S Chung, and
David M Kaye, and
John Blair, and
Jean-Christophe Eicher, and
Scott L Hummel, and
Andreas Zirlik, and
Ralf Westenfeld, and
Christopher Hayward, and
Thomas M Gorter, and
Catherine Demers, and
Ranjith Shetty, and
Gregory Lewis, and
Randall C Starling, and
Sanjay Patel, and
Deepak K Gupta, and
Hakim Morsli, and
Martin Penicka, and
Maja Cikes, and
Finn Gustafsson, and
Frank E Silvestry, and
Ethan J Rowin, and
Donald E Cutlip, and
Martin B Leon, and
Dalane W Kitzman, and
Franz X Kleber, and
Sanjiv J Shah, and
Medical University of South Carolina, Charleston, South Carolina, USA; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina, USA. Electronic address: litwins@musc.edu.
Many patients with heart failure and preserved ejection fraction have no overt volume overload and normal resting left atrial (LA) pressure. This study sought to characterize patients with normal resting LA pressure (pulmonary capillary wedge pressure [PCWP] <15 mm Hg) but exercise-induced left atrial hypertension (EILAH). The REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trial randomized 626 patients with ejection fraction ≥40% and exercise PCWP ≥25 mm Hg to atrial shunt or sham procedure. The primary trial outcome, a hierarchical composite of death, heart failure hospitalization, intensification of diuretics, and change in health status was compared between patients with EILAH and those with heart failure and resting left atrial hypertension (RELAH). Patients with EILAH (29%) had similar symptom severity, but lower natriuretic peptide levels, higher 6-minute walk distance, less atrial fibrillation, lower left ventricular mass, smaller LA volumes, lower E/e', and better LA strain. PCWP was lower at rest, but had a larger increase with exercise in EILAH. Neither group as a whole had a significant effect from shunt therapy vs sham. Patients with EILAH were more likely to have characteristics associated with atrial shunt responsiveness (peak exercise pulmonary vascular resistance <1.74 WU) and no pacemaker (63% vs 46%; P < 0.001). The win ratio for the primary outcome was 1.56 (P = 0.08) in patients with EILAH and 1.51 (P = 0.04) in those with RELAH when responder characteristics were present. Patients with EILAH had similar symptom severity but less advanced myocardial and pulmonary vascular disease. This important subgroup may be difficult to diagnose without invasive exercise hemodynamics, but it has characteristics associated with favorable response to atrial shunt therapy. (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure [REDUCE LAP-HF TRIAL II]; NCT03088033).
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