PMID- 34461042 OWN - NLM STAT- MEDLINE DCOM- 20210928 LR - 20211108 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 398 IP - 10304 DP - 2021 Sep 11 TI - Haemodynamic-guided management of heart failure (GUIDE-HF): a randomised controlled trial. PG - 991-1001 LID - S0140-6736(21)01754-2 [pii] LID - 10.1016/S0140-6736(21)01754-2 [doi] AB - BACKGROUND: Previous studies have suggested that haemodynamic-guided management using an implantable pulmonary artery pressure monitor reduces heart failure hospitalisations in patients with moderately symptomatic (New York Heart Association [NYHA] functional class III) chronic heart failure and a hospitalisation in the past year, irrespective of ejection fraction. It is unclear if these benefits extend to patients with mild (NYHA functional class II) or severe (NYHA functional class IV) symptoms of heart failure or to patients with elevated natriuretic peptides without a recent heart failure hospitalisation. This trial was designed to evaluate whether haemodynamic-guided management using remote pulmonary artery pressure monitoring could reduce heart failure events and mortality in patients with heart failure across the spectrum of symptom severity (NYHA funational class II-IV), including those with elevated natriuretic peptides but without a recent heart failure hospitalisation. METHODS: The randomised arm of the haemodynamic-GUIDEed management of Heart Failure (GUIDE-HF) trial was a multicentre, single-blind study at 118 centres in the USA and Canada. Following successful implantation of a pulmonary artery pressure monitor, patients with all ejection fractions, NYHA functional class II-IV chronic heart failure, and either a recent heart failure hospitalisation or elevated natriuretic peptides (based on a-priori thresholds) were randomly assigned (1:1) to either haemodynamic-guided heart failure management based on pulmonary artery pressure or a usual care control group. Patients were masked to their study group assignment. Investigators were aware of treatment assignment but did not have access to pulmonary artery pressure data for control patients. The primary endpoint was a composite of all-cause mortality and total heart failure events (heart failure hospitalisations and urgent heart failure hospital visits) at 12 months assessed in all randomly assigned patients. Safety was assessed in all patients. A pre-COVID-19 impact analysis for the primary and secondary outcomes was prespecified. This study is registered with ClinicalTrials.gov, NCT03387813. FINDINGS: Between March 15, 2018, and Dec 20, 2019, 1022 patients were enrolled, with 1000 patients implanted successfully, and follow-up was completed on Jan 8, 2021. There were 253 primary endpoint events (0.563 per patient-year) among 497 patients in the haemodynamic-guided management group (treatment group) and 289 (0.640 per patient-year) in 503 patients in the control group (hazard ratio [HR] 0.88, 95% CI 0.74-1.05; p=0.16). A prespecified COVID-19 sensitivity analysis using a time-dependent variable to compare events before COVID-19 and during the pandemic suggested a treatment interaction (p(interaction)=0.11) due to a change in the primary endpoint event rate during the pandemic phase of the trial, warranting a pre-COVID-19 impact analysis. In the pre-COVID-19 impact analysis, there were 177 primary events (0.553 per patient-year) in the intervention group and 224 events (0.682 per patient-year) in the control group (HR 0.81, 95% CI 0.66-1.00; p=0.049). This difference in primary events almost disappeared during COVID-19, with a 21% decrease in the control group (0.536 per patient-year) relative to pre-COVID-19, virtually no change in the treatment group (0.597 per patient-year), and no difference between groups (HR 1.11, 95% CI 0.80-1.55; p=0.53). The cumulative incidence of heart failure events was not reduced by haemodynamic-guided management (0.85, 0.70-1.03; p=0.096) in the overall study analysis but was significantly decreased in the pre-COVID-19 impact analysis (0.76, 0.61-0.95; p=0.014). 1014 (99%) of 1022 patients had freedom from device or system-related complications. INTERPRETATION: Haemodynamic-guided management of heart failure did not result in a lower composite endpoint rate of mortality and total heart failure events compared with the control group in the overall study analysis. However, a pre-COVID-19 impact analysis indicated a possible benefit of haemodynamic-guided management on the primary outcome in the pre-COVID-19 period, primarily driven by a lower heart failure hospitalisation rate compared with the control group. FUNDING: Abbott. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Lindenfeld, JoAnn AU - Lindenfeld J AD - Vanderbilt Heart and Vascular Institute, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: joann.lindenfeld@vumc.org. FAU - Zile, Michael R AU - Zile MR AD - Medical University of South Carolina, RJH Department of Veterans Affairs Medical Center, Charleston, SC, USA. FAU - Desai, Akshay S AU - Desai AS AD - Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. FAU - Bhatt, Kunjan AU - Bhatt K AD - Austin Heart, Austin, TX, USA. FAU - Ducharme, Anique AU - Ducharme A AD - Montreal Heart Institute, Universite de Montreal, Montreal, QC, Canada. FAU - Horstmanshof, Douglas AU - Horstmanshof D AD - Integris Baptist Medical Center, Oklahoma City, OK, USA. FAU - Krim, Selim R AU - Krim SR AD - John Ochsner Heart and Vascular Institute, Ochsner Medical Center, New Orleans, LA, USA. FAU - Maisel, Alan AU - Maisel A AD - University of California San Diego, La Jolla, CA, USA. FAU - Mehra, Mandeep R AU - Mehra MR AD - Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. FAU - Paul, Sara AU - Paul S AD - Catawba Valley Health System, Conover, NC, USA. FAU - Sears, Samuel F AU - Sears SF AD - East Carolina University, Greenville, NC, USA. FAU - Sauer, Andrew J AU - Sauer AJ AD - University of Kansas School of Medicine, Kansas City, KS, USA. FAU - Smart, Frank AU - Smart F AD - Louisiana State University School of Medicine, New Orleans, LA, USA. FAU - Zughaib, Marcel AU - Zughaib M AD - Providence Hospital, Southfield, MI, USA. FAU - Castaneda, Paige AU - Castaneda P AD - Austin Heart, Austin, TX, USA. FAU - Kelly, Jean AU - Kelly J AD - Providence Hospital, Southfield, MI, USA. FAU - Johnson, Nessa AU - Johnson N AD - Abbott, Abbott Park, IL, USA. FAU - Sood, Poornima AU - Sood P AD - Abbott, Abbott Park, IL, USA. FAU - Ginn, Greg AU - Ginn G AD - Abbott, Abbott Park, IL, USA. FAU - Henderson, John AU - Henderson J AD - Abbott, Abbott Park, IL, USA. FAU - Adamson, Philip B AU - Adamson PB AD - Abbott, Abbott Park, IL, USA. FAU - Costanzo, Maria Rosa AU - Costanzo MR AD - Advocate Heart Institute, Naperville, IL, USA. LA - eng SI - ClinicalTrials.gov/NCT03387813 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210827 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R SB - IM CIN - Lancet. 2021 Sep 11;398(10304):935-936. PMID: 34461039 MH - Aged MH - COVID-19 MH - *Electrodes, Implanted MH - Female MH - *Heart Failure/classification/physiopathology MH - *Hemodynamics/physiology MH - Hospitalization/*statistics & numerical data/trends MH - Humans MH - Male MH - Mortality/trends MH - *Pulmonary Artery MH - Remote Sensing Technology COIS- Declaration of interests JL has received research grants from AstraZeneca, Sensible Medical, and Volumetrix and is a consultant for Abbott, Alleviant Medical, AstraZeneca, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards, Impulse Dynamics, and VWave. ASD has received research grants from Alnylam, AstraZeneca, Bayer, and Novartis, is a consultant for Abbott and Alnylam, AstraZeneca, Amgen, Biofourmis, Boston Scientific, Boehringer Ingelheim, Cytokinetics, DalCor Pharma, Lexicon, Merck, Novartis, Relypsa, and Regeneron, and has received personal fees from Lupin Pharma and Sun Pharma. KB is a consultant for Abbott and has received personal fees from Pfizer and Novartis. DH is a consultant for Abbott, has received personal fees from Abbott, and has served on advisory boards for Abbott. SRK is a consultant for Abbott and CareDx and has received personal fees from Abbott and CareDx. MRM is a consultant for Abbott, Medtronic, Janssen, Portola, Bayer, Triple Gene, and Baim Institute for Clinical Research, has served on advisory boards for Abbott and Mesoblast, has served on the Clinical Events Committee for GUIDE-HF through the Baim Institute for Clinical Research, and has stock in NuPulseCV, Leviticus, and FineHeart. SFS has received research grants from Medtronic and Zoll, is a consultant for Abbott, Medtronic, and Milestone Pharmaceuticals, and has received personal fees from Medtronic and Zoll. AJS is a consultant for Abbott and has received personal fees from Abbott. FS has received research grants from Amgen and is a consultant for Abbott. MRZ, AD, AM, SP, and MRC are consultants for Abbott. NJ, PS, GG, JH, and PBA are employees of Abbott. All other authors declare no competing interests. EDAT- 2021/08/31 06:00 MHDA- 2021/09/29 06:00 CRDT- 2021/08/30 20:10 PHST- 2021/06/10 00:00 [received] PHST- 2021/07/23 00:00 [revised] PHST- 2021/07/27 00:00 [accepted] PHST- 2021/08/31 06:00 [pubmed] PHST- 2021/09/29 06:00 [medline] PHST- 2021/08/30 20:10 [entrez] AID - S0140-6736(21)01754-2 [pii] AID - 10.1016/S0140-6736(21)01754-2 [doi] PST - ppublish SO - Lancet. 2021 Sep 11;398(10304):991-1001. doi: 10.1016/S0140-6736(21)01754-2. Epub 2021 Aug 27.