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.

中文翻译：

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血流动力学指导的心力衰竭管理 (GUIDE-HF)：一项随机对照试验

背景

先前的研究表明，使用植入式肺动脉压力监测器进行血流动力学指导管理可减少中度症状（纽约心脏协会 [NYHA] 功能等级 III）慢性心力衰竭患者的心力衰竭住院率和过去一年的住院率，无论射血分数。目前尚不清楚这些益处是否适用于轻度（NYHA 功能等级 II）或重度（NYHA 功能等级 IV）心力衰竭症状的患者，或近期未因心力衰竭住院治疗的利钠肽升高的患者。

方法

血液动力学指南心力衰竭管理 (GUIDE-HF) 试验的随机组是一项在美国和加拿大 118 个中心进行的多中心、单盲研究。在成功植入肺动脉压力监测器后，随机分配具有所有射血分数、NYHA 功能 II-IV 级慢性心力衰竭以及近期心力衰竭住院或利钠肽升高（基于先验阈值）的患者（1 :1) 到基于肺动脉压的血流动力学指导的心力衰竭管理或常规护理对照组。患者对他们的研究组分配不知情。研究人员知道治疗分配，但无法获得对照患者的肺动脉压数据。主要终点是 12 个月时在所有随机分配的患者中评估的全因死亡率和总心力衰竭事件（心力衰竭住院和紧急心力衰竭住院）的复合终点。在所有患者中评估了安全性。预先指定了对主要和次要结果的 COVID-19 影响分析。本研究已在 ClinicalTrials.gov 注册，NCT03387813。

发现

2018年3月15日至2019年12月20日共入组1022例患者，其中1000例成功植入，2021年1月8日完成随访。主要终点事件253次（0·563/患者年）血液动力学指导管理组（治疗组）中的 497 名患者和对照组 503 名患者中的 289 名（每患者年 0·640）（风险比 [HR] 0·88，95% CI 0·74–1 ·05；p=0·16）。使用时间相关变量来比较 COVID-19 之前和大流行期间的事件的预先指定的 COVID-19 敏感性分析表明治疗相互作用（p_相互作用=0·11) 由于在试验的大流行阶段主要终点事件发生率发生了变化，因此需要进行 COVID-19 之前的影响分析。在 COVID-19 之前的影响分析中，干预组有 177 起主要事件（每患者年 0·553），对照组有 224 起事件（每患者年 0·682）（HR 0·81， 95% CI 0·66–1·00；p=0·049）。这种主要事件的差异在 COVID-19 期间几乎消失，与 COVID-19 之前相比，对照组减少了 21%（每患者年 0·536），治疗组几乎没有变化（0·597/患者年）。患者年），组间无差异（HR 1·11，95% CI 0·80–1·55；p=0·53）。血流动力学指导的管理并未降低心力衰竭事件的累积发生率 (0·85, 0·70–1·03; p=0·096) 在整体研究分析中，但在 COVID-19 之前的影响分析中显着下降 (0·76, 0·61–0·95; p=0·014)。1022 名患者中有 1014 名 (99%) 没有设备或系统相关并发症。

解释

在整体研究分析中，与对照组相比，血液动力学指导的心力衰竭管理并未导致死亡率和总心力衰竭事件的复合终点率降低。然而，COVID-19 之前的影响分析表明，血液动力学指导管理对 COVID-19 之前的主要结果可能有好处，这主要是由于与对照组相比心力衰竭住院率较低。

资金

雅培。