Haemodynamic Guided Heart Failure Management as a Hospitalization Reduction Strategy – the GUIDE-HF Tria

KEY POINTS:

· CardioMEMS, a wireless, battery-free pressure sensor implanted in the pulmonary artery that transmits real-time pressure data, is an established means of remote, longitudinal clinical assessment for ambulatory patients with symptomatic heart failure syndromes

· The benefits of CardioMEMS in patients across the spectrum of heart failure syndrome classes was previously unknown

· GUIDE-HF shows that the benefits of hemodynamic guided management extends to a larger group of heart failure patients including patients with New York Heart Association Class II-IV heart failure, those without prior heart failure hospitalization, and among patients with all ejection fractions

Heart failure is a chronic, progressive condition that typically worsens over time. As a result it is one of the leading causes of hospitalization in the United States, resulting in almost one million hospitalizations in this country annually. Pulmonary artery congestion is the cause of many associated symptoms and therefore has been a long-standing target of therapeutic intervention. One such tool is the CardioMEMS HF System (Abbot, Atlanta, GA), a wireless, battery-free sensor that is implanted into the pulmonary artery to transmit pulmonary artery pressures. The device allows clinicians to

titrate heart failure medications according to the data received from the device, thereby allowing optimal control over fluid levels and ideally preventing heart failure hospitalizations for pulmonary congestion. Previously, the CardioMEMS device had been approved in Europe and the US on the basis of the results of the CHAMPION Trial, which demonstrated that active heart failure management guided by remotely obtained PA pressures using CardioMEMS reduced heart failure hospitalizations and improved health-related quality of life only in patients with more advanced heart syndromes, defined as patients with New York Heart Association (NYHA) Class III heart failure with

an admission for heart failure in the previous year. Notably this improvement was seen in patients irrespective of ejection fraction, therefore providing clinicians with possible therapeutic targets across the spectrum of heart failure syndromes.

The haemodynamic-GUIDEed management of Heart Failure (GUIDE-HF) trial, presented August 27th, 2021 in a Hot Line Session at ESC Congress sought to determine whether other types of patients might benefit from this pulmonary artery pressure monitoring device. Specifically, they evaluated whether haemodynamic-guided management using CardioMEMS could reduce heart failure events and mortality in patients with heart failure across the range of symptom severity (NYHA functional class II–IV), including those with elevated biomarkers but without a recent heart failure hospitalization. Furthermore, whether remote monitoring of pulmonary artery pressures could lead to timely intervention that might actually improve mortality is unknown.

The GUIDE-HF Trail was a multicenter, single-blind study conducted at 118 centers in the USA and Canada. Following successful implantation of a pulmonary artery pressure monitor, 1,000 patients with both preserved and reduced ejection fractions, NYHA functional class II–IV chronic heart failure, and either a recent heart failure hospitalization or elevated natriuretic peptides (based on a-priori thresholds) were randomly assigned (1:1) to either haemodynamic-guided heart failure management based on transmitted pulmonary artery pressures or to a control group who did not have pulmonary artery pressure data available. Though patients were blinded to the treatment allocation investigators were not. However, investigators 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 (including heart failure hospitalizations and urgent heart failure hospital visits) at 12 months assessed in all randomly assigned patients. A pre-COVID-19 impact analysis for the primary and secondary outcomes was prespecified. The details of the study’s methods were published in the American Heart Journal in August 2019 and further information can be found at ClinicalTrials.gov (NCT03387813).

The trial’s results showed that though the primary endpoint was not met for the overall analysis (HR 0.88, 95% CI 0.74-1.05, p=0.16), the primary endpoint was met in the pre-COVID-19 impact analysis alone (HR 0.81, 95% CI 0.66-1.00, p=0.049). Furthermore

there was a highly significant 28% reduction in heart failure hospitalizations for patients with CardioMEMS devices in the pre-COVID-19 impact analysis (HR 0.72, 95% CI 0.57-0.92, p=0.007). This data is consistent with results previously reported in the CHAMPION trial, which enrolled only NYHA Class III patients with a previous heart failure hospitalization. Overall, there was a consistent signal for benefit for hemodynamic guided monitoring for patients of all subgroups regardless of NYHA Class, ejection fraction, sex, biomarkers, heart failure hospitalization in prior year, age, race, or etiology of heart failure. Notably there were only 54 NYHA class IV patients enrolled in the study and results for this population were inconsistent.

 

The trial’s lead investigator, Dr. Lindenfeld, points out during the GUIDE-HF press presentation that this trial’s novel finding is that it shows significant reduction in heart failure hospitalizations for patients with NYHA class II symptoms with a prior heart failure hospitalization or elevated biomarkers, NYHA class III patients even without a prior heart failure hospitalizations though with elevated biomarkers, and for patients with all ejection fractions. Furthermore, the findings have important implications for patients with heart failure with preserved ejection fractions as few therapies have shown benefit for this group.

The associated manuscript for this study is published today in The Lancet https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01754-2/fulltext.