Elsevier

JACC: Heart Failure

Volume 11, Issue 8, Part 2, August 2023, Pages 1103-1117
JACC: Heart Failure

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

https://doi.org/10.1016/j.jchf.2023.01.030Get rights and content

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)

Section snippets

REDUCE LAP-HF II study design and objectives

The objectives and design of the REDUCE LAP-HF II study have been previously described in detail.3 Briefly, REDUCE LAP-HF II was a multicenter, international, randomized, double-blind, sham-controlled trial of the Corvia Atrial Shunt in adults with HF and LVEF ≥40%. After comprehensive noninvasive and invasive hemodynamic screening, eligible participants were randomly assigned 1:1 to receive the Corvia Atrial Shunt (IASD System II) or a sham control procedure.5,6 The primary endpoint was a

Enrollment of REDUCE LAP II study participants

Patients in the EILAH group were slightly younger, with similar distribution of sex, race/ethnicity, and obesity (Table 1). The EILAH group was less likely to have hypertension, diabetes, chronic kidney disease, and current or prior atrial fibrillation. Patients with EILAH had higher estimated glomerular filtration rate, lower use of loop diuretic agents and beta-adrenergic blocking agents, but higher use of mineralocorticoid receptor agonists (Table 1, Supplemental Table 1).

NYHA functional

Discussion

In this large, randomized trial of a novel device therapy in hemodynamically defined HFpEF, almost one-third of subjects had a resting PCWP <15 mm Hg but elevation of PCWP to ≥25 mm Hg with supine exercise. Symptom severity was similar in the groups with normal or elevated resting PCWP (both groups predominantly NYHA functional class III with similar KCCQ clinical summary score). However, those with EILAH had ∼50% lower natriuretic peptide levels; fewer comorbidities; and many clinical,

Conclusions

In a large, rigorously phenotyped cohort of patients with hemodynamically verified HFpEF or HF with mildly reduced ejection fraction, almost one-third had normal LV filling pressures at rest. Exercise evaluation is necessary to unmask the underlying cardiac limitations in these patients. Although they have significant impairment of quality of life, these patients appear to have a less advanced stage of myocardial and pulmonary vascular dysfunction. Importantly, they have a number of

Funding Support and Author Disclosures

This study was sponsored by Corvia Medical Inc. Dr Litwin has received research funding from the department of Veterans Affairs, Corvia, AstraZeneca, V-Wave, Axon Therapeutics, and Eli Lilly all paid to the institution; has received consulting fees from CVRx, Axon Therapeutics, Occlutech, Eli Lilly, and Rivus Pharmaceuticals; and has received travel grants, speaker fees, and advisory board honoraria from NovoNordisk and Roche. Dr Komtebedde is employed by Corvia. Dr Burkhoff has consulted for

References (22)

  • B.A. Borlaug et al.

    Latent pulmonary vascular disease may alter the response to therapeutic atrial shunt device in heart failure

    Circulation

    (2022)
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