Reviwer: Dr. Duygu İnan

Name of the study : Haemodynamic-guided management of heart failure (GUIDE-HF): a randomised controlled trial

Presented congress : 2021 ESC/EAST

Link : https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01754-2/fulltext

Background :

Pulmonary congestion is a major cause of reduced functional capacity, poor quality of life, recurrent heart failure hospitalizations and increased mortality in patients with heart failure. Elevated or increasing pulmonary artery pressure predicts congestion and can be tracked longitudinally with implantable devices. Previous studies have showed that haemodynamic-guided management using an implantable pulmonary artery pressure monitor (CardioMEMS) reduces heart failure hospitalizations in patients with New York Heart Association (NYHA) functional class III heart failure and a hospitalization in the past year, independent of ejection fraction. It is unclear whether these benefits can be achieved in patients with NYHA functional class II or NYHA functional class IV symptoms of heart failure and elevated natriuretic peptides without a recent heart failure hospitalization.

Objective :

This trial was designed to assess the safety and efficacy of haemodynamic-guided management using remote pulmonary artery pressure monitoring 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.

Method :

This trial was a multicentre, single-blind study at 118 centres in the USA and Canada. 1,000 patients were enrolled with NYHA class II–IV heart failure and either a hospitalisation for heart failure within the preceding 12 months or elevated natriuretic peptide levels within 30 days prior to consent to participate in the study. All patients had a pulmonary artery pressure  monitor implanted. Patients were then randomized in a single-blind 1:1 fashion to either hemodynamic monitoring and titration based on PA pressures (n = 497) or standard of care HF management (n = 503). Patients were blinded to the treatment allocation but the investigators were not blinded without accessing to pulmonary artery pressure data for control patients. The primary endpoint was a composite of all-cause mortality and total heart failure events  at 12 months. Safety was assessed in all patients. A pre-COVID-19 impact analysis for the primary and secondary outcomes was prespecified.

Results :

During a median follow-up of 11.7 months, 253 primary endpoint events occurred in the hemodynamic-monitoring group and 289 in the usual care group. In the overall analysis, the primary endpoint was reduced by 12% in the hemodynamic-monitoring group but did not meet statistical significance (hazard ratio [HR] 0.88; 95% confidence interval [CI] 0.74–1.05; p=0.16). However, a prespecified COVID-19 impact analysis demonstrated a significant interaction warranting a pre-COVID-19 analysis. The pre-COVID-19 analysis demonstrated a significant 19% reduction in primary endpoint events in the hemodynamic-monitoring group (HR 0.81; CI 0.66–1.00; p=0.0489). The cumulative incidence of heart failure events was not reduced by haemodynamic-guided management (HR 0·85, CI 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 :

There is no difference in cardiovascular  outcomes among stable outpatients with chronic HF when comparing hemodynamic-guided management to usual care. 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 usual care group. Indeed, it is clear that the COVID-19 pandemic has impacted GUIDE-HF outcomes. This result shows us that statistical analysis plans should be adjusted to take into account the real effects of clinical trials conducted during pandemics. Most people currently measure their daily steps and monitor their heart rate with Apple Watch, which shows that people are investing in their health and demand actionable information. This study was designed primarily as part of this desire, as well as guiding physicians, to both keep patients out of the hospital and better understand how they respond to medication. GUIDE-HF results are encouraging but inconclusive in this regard and should inform further research, possibly a large, simple, open-label trial to investigate a system of care rather than a single technology.