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

Borlaug, B. A. et al. (2022) Latent pulmonary vascular disease may alter the response to therapeutic atrial shunt device in heart failure. Circulation, (doi: 10.1161/CIRCULATIONAHA.122.059486) (PMID:35354306) (Early Online Publication)

[img] Text
267795.pdf - Accepted Version
Restricted to Repository staff only until 30 September 2022.

883kB

Abstract

Background: In the REDUCE LAP-HF II trial, implantation of an atrial shunt device did not provide, overall, clinical benefit for patients with heart failure and preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). However, pre-specified analyses identified differences in response in subgroups defined by pulmonary artery systolic pressure during submaximal exercise, right atrial (RA) volume, and sex. Shunt implantation reduces left atrial (LA) pressures but increases pulmonary blood flow, which may be poorly tolerated in patients with pulmonary vascular disease (PVD). Based upon these results, we hypothesized that patients with latent PVD, defined as elevated pulmonary vascular resistance (PVR) during exercise, might be harmed by shunt implantation, and conversely that patients without PVD might benefit. Methods: REDUCE LAP-HF II enrolled 626 patients with HF, EF ≥40%, exercise pulmonary capillary wedge pressure ≥25 mmHg, and resting PVR <3.5 WU who were randomized 1:1 to atrial shunt device or sham control. The primary outcome, a hierarchical composite of cardiovascular death, nonfatal ischemic stroke, recurrent HF events, and change in health status, was analyzed using the win ratio. Latent PVD was defined as PVR ≥1.74 WU (highest tertile) at peak exercise, measured prior to randomization. Results: Compared to patients without PVD (n=382), those with latent PVD (n=188) were older, had more atrial fibrillation and right heart dysfunction, and were more likely to have elevated LA pressure at rest. Shunt treatment was associated with worse outcomes in patients with PVD (win ratio 0.60, [95% CI 0.42, 0.86]; p=0.005) and signal of clinical benefit in patients without PVD (win ratio 1.31 [95% CI 1.02, 1.68]; p=0.038). Patients with larger RA volumes and men had worse outcomes with the device, and both groups were more likely to have pacemakers, HFmrEF, and increased LA volume. For patients without latent PVD or pacemaker (n=313, 50% of randomized patients), shunt treatment resulted in more robust signal of clinical benefit (win ratio 1.51 [95% CI 1.14, 2.00]; p=0.004). Conclusions: In patients with HFpEF/HFmrEF, the presence of latent PVD uncovered by invasive hemodynamic exercise testing identifies patients who may worsen with atrial shunt therapy, whereas those without latent PVD may benefit.

Item Type:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Petrie, Professor Mark and Cleland, Professor John
Authors: Borlaug, B. A., Blair, J., Bergmann, M. W., Bugger, H., Burkhoff, D., Bruch, L., Celermajer, D. S., Claggett, B., Cleland, J. G. F., Cutlip, D. E., Dauber, I., Eicher, J.-C., Gao, Q., Gorter, T. M., Gustafsson, F., Hayward, C., Van der Heyden, J., Hasenfuß, G., Hummel, S. L., Kaye, D. M., Komtebedde, J., Massaro, J. M., Mazurek, J. A., McKenzie, S., Mehta, S. R., Petrie, M. C., Post, M. C., Nair, A., Rieth, A., Silvestry, F. E., Solomon, S. D., Trochu, J.-N., Veldhuisen, D. J. V., Westenfeld, R., Leon, M. B., and Shah, S. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Circulation
Publisher:American Heart Association
ISSN:0009-7322
ISSN (Online):1524-4539
Published Online:31 March 2022
Copyright Holders:Copyright © 2021 American Heart Association, Inc.
First Published:First published in Circulation 2022
Publisher Policy:Reproduced in accordance with the publisher copyright policy

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science