Exercise-Induced Left Atrial Hypertension in Heart Failure With Preserved Ejection Fraction

Sheldon E Litwin; Jan Komtebedde; Mo Hu; Daniel Burkhoff; Gerd Hasenfuß; Barry A Borlaug; Scott D Solomon; Michael R Zile; Rajeev C Mohan; Rami Khawash; Aaron L Sverdlov; Peter Fail; Eugene S Chung; David M Kaye; John Blair; Jean-Christophe Eicher; Scott L Hummel; Andreas Zirlik; Ralf Westenfeld; Christopher Hayward; Thomas M Gorter; Catherine Demers; Ranjith Shetty; Gregory Lewis; Randall C Starling; Sanjay Patel; Deepak K Gupta; Hakim Morsli; Martin Penicka; Maja Cikes; Finn Gustafsson; Frank E Silvestry; Ethan J Rowin; Donald E Cutlip; Martin B Leon; Dalane W Kitzman; Franz X Kleber; Sanjiv J Shah; REDUCE LAP-HF Investigators and Research Staff

doi:10.1016/j.jchf.2023.01.030

Exercise-Induced Left Atrial Hypertension in Heart Failure With Preserved Ejection Fraction

JACC Heart Fail. 2023 Aug;11(8 Pt 2):1103-1117. doi: 10.1016/j.jchf.2023.01.030. Epub 2023 Mar 20.

Authors

Sheldon E Litwin¹, Jan Komtebedde², Mo Hu³, Daniel Burkhoff⁴, Gerd Hasenfuß⁵, Barry A Borlaug⁶, Scott D Solomon⁷, Michael R Zile⁸, Rajeev C Mohan⁹, Rami Khawash¹⁰, Aaron L Sverdlov¹¹, Peter Fail¹², Eugene S Chung¹³, David M Kaye¹⁴, John Blair¹⁵, Jean-Christophe Eicher¹⁶, Scott L Hummel¹⁷, Andreas Zirlik¹⁸, Ralf Westenfeld¹⁹, Christopher Hayward²⁰, Thomas M Gorter²¹, Catherine Demers²², Ranjith Shetty²³, Gregory Lewis²⁴, Randall C Starling²⁵, Sanjay Patel²⁶, Deepak K Gupta²⁷, Hakim Morsli²⁸, Martin Penicka²⁹, Maja Cikes³⁰, Finn Gustafsson³¹, Frank E Silvestry³², Ethan J Rowin³³, Donald E Cutlip³⁴, Martin B Leon⁴, Dalane W Kitzman³⁵, Franz X Kleber³⁶, Sanjiv J Shah³; REDUCE LAP-HF Investigators and Research Staff

Affiliations

¹ 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.
² Corvia Medical Inc, Tewksbury, Massachusetts, USA.
³ Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
⁴ Cardiovascular Research Foundation, New York City, New York, USA.
⁵ University of Göttingen, Göttingen, Germany.
⁶ Mayo Clinic, Rochester, Minnesota, USA.
⁷ Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁸ Medical University of South Carolina, Charleston, South Carolina, USA; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina, USA.
⁹ Scripps Health, La Jolla, California, USA.
¹⁰ The Ohio State University, Columbus, Ohio, USA.
¹¹ John Hunter Hospital, New Castle, New South Wales, Australia; University of Newcastle, New Castle, New South Wales, Australia.
¹² Cardiovascular Institute of the South, Houma, Louisiana, USA.
¹³ Christ Hospital, Cincinnati, Ohio, USA.
¹⁴ Alfred Hospital, Melbourne, Australia.
¹⁵ University of Chicago, Chicago, Illinois, USA.
¹⁶ Centre Hospitalier Universitaire de Dijon-Hôpital Bocage Central, Dijon, France.
¹⁷ University of Michigan Health Systems, Ann Arbor, Michigan, USA; Veterans Affairs Ann Arbor, Ann Arbor, Michigan, USA.
¹⁸ University of Graz, Graz, Austria.
¹⁹ Division of Cardiology, Pulmonology, and Vascular Medicine Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
²⁰ St Vincent Hospital Sydney, Sydney, Australia.
²¹ University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
²² McMaster University and Hamilton Health Sciences, Hamilton, Canada.
²³ University of Arizona, Arizona, USA.
²⁴ Massachusetts General Hospital, Boston, Massachusetts, USA.
²⁵ Cleveland Clinic, Cleveland, Ohio, USA.
²⁶ Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; Sydney Medical School, The University of Sydney, New South Wales, Australia; The Heart Research Institute, Sydney, New South Wales, Australia.
²⁷ Vanderbilt University Medical Center, Nashville, Tennessee, USA.
²⁸ Sarasota Memorial Hospital, Sarasota, Florida, USA.
²⁹ Onze Lieve Vrouwen Ziekenhuis, Aalst, Belgium.
³⁰ Department of Cardiovascular Diseases, University of Zagreb School of Medicine and University Hospital Center, Zagreb, Croatia.
³¹ Rigshospitalet Copenhagen, Copenhagen, Denmark.
³² University of Pennsylvania, Philadelphia, Pennsylvania, USA.
³³ Tufts University, Boston, Massachusetts, USA.
³⁴ Baim Clinical Research Institute, Boston, Massachusetts, USA.
³⁵ Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
³⁶ Martin-Luther-University, Halle-Wittenberg, Germany.

PMID: 36939661
DOI: 10.1016/j.jchf.2023.01.030

Abstract

Background: Many patients with heart failure and preserved ejection fraction have no overt volume overload and normal resting left atrial (LA) pressure.

Objectives: 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).

Methods: 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).

Results: 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.

Conclusions: 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).

Keywords: exercise capacity; exercise hemodynamics; heart failure with preserved ejection fraction; pulmonary capillary wedge pressure; randomized controlled trial.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Atrial Fibrillation* / complications
Atrial Fibrillation* / therapy
Cardiac Catheterization
Heart Failure* / complications
Heart Failure* / diagnosis
Heart Failure* / therapy
Humans
Hypertension*
Stroke Volume / physiology
Ventricular Function, Left

Associated data

ClinicalTrials.gov/NCT03088033

Abstract

Publication types

MeSH terms

Associated data

Grants and funding