Hemodynamic heart failure (HF) management did not reduce either mortality or rates of HF events compared with guideline-managed treatment in patients with mild or severe HF, according to research results published in the Lancet.
While previous studies have indicated that hemodynamic-guided HF management can reduce HF hospitalizations in moderately symptomatic patients with chronic HF (NYHA Class III), it is still unclear whether these benefits can be extended to patients with mild or severe HF symptoms (NYHA Class II and IV, respectively).
Using the randomized arm of the GUIDE-HF trial (ClinicalTrials.gov Identifier: NCT03387813), researchers compared HF management guided by remote pulmonary artery pressure measurements made via an implanted sensor with standard-of-care HF management through guideline recommended medical therapy.
Patients with NHYA functional class II through IV with a HF hospitalization in the previous 12 months were enrolled, regardless of left ventricular ejection fraction (LVEF). After successful implantation of a pulmonary artery pressure sensor (CardioMEMS; Abbott), patients were randomly assigned 1:1 to either the treatment group or the guideline-managed control group.
All patients underwent clinical assessments at 6 and 12 months postimplantation, including quality of life, safety, and functional assessments. The primary study outcome was a composite of all-cause mortality and total HF events (hospitalizations and urgent HF hospital visits) at 12 months. Secondar effectiveness outcomes were cumulative HF events at 12 months, health status at 6 and 12 months, and functional status at 6 and 12 months (assessed via 6-min hall walk test [6MHW]), as well as individual components of the primary endpoint at month 12.
The total study cohort included 1000 patients, 497 of whom were assigned to treatment (control n=503). A total of 30% of patients from the entire cohort were NYHA Class II, 65% were NYHA Class III, and 5% were NYHA Class IV. Enrollment was due to previous HF hospitalization (36%), elevated natriuretic peptides (44%), or both (20%).
Overall, 253 and 289 primary endpoint events were recorded in the treatment and control groups, respectively (hazard ratio [HR], 0.88; 95% CI, 0.74-1.05). A total of 185 and 225 HF hospitalizations were recorded in each group (HR, 0.83; 95% CI, 0.68-1.01), with no significant between-group difference in either urgent HF hospital visits or mortality.
Results of a prespecified COVID-19 sensitivity analysis indicated that there was an effect of COVID-19 on the primary endpoint, which warranted an analysis of all endpoints prior to the March 13, 2020 US national emergency declaration. This pre-COVID-19 impact analysis showed a reduction in primary endpoint events of 177 and 224 events in the treatment and control groups (HR, 0.81; 95% CI, 0.66-1.00). HF hospitalizations were also reduced (124 vs 176; HR, 0.72; 95% CI, 0.57-0.92). No between-group differences were noted for urgent HF hospital visits or all-cause mortality prior to COVID-19.
Subgroup analysis results showed that in terms of the primary endpoint, the HR was consistent for most subgroups. Interaction’s for the primary outcome were suggested for NYHA functional class, with a greater treatment effect in NYHA Class II or II vs Class IV), race, and sex (greater treatment effect for Black patients and women).
While there were noticeably lower event rates in certain subgroups—including those who qualified due to elevated BNP or NT-proBNP levels—a consistent HR for the primary endpoint was noted.
Regarding secondary endpoints, there were 213 and 252 total HF events in each group (HR, 0.85; 95% CI, 0.70-1.03). In the pre-COVID-19 impact analysis, investigators identified 147 and 199 HF events in the treatment and control groups (HR, 0.76; 95% CI, 0.61-0.95). In both the overall and pre-COVID-19 analyses, health status scores improved in both groups at 6 months. No difference was noted in the 6MHW either within or between groups in either analysis.
There was a significantly lower area under the pressure-time curve (AUC) for mean pulmonary artery pressure in the treatment vs the control group in the overall analysis; mean pulmonary artery pressure AUC was -792.8 mmHg in the treatment group and -582.9 mmHg in the control group. The pre-COVID-19 analysis also demonstrated a lower mean pulmonary artery pressure AUC (-518.0 mmHg vs -342.2 mmHg), with a gradually widening difference over time in favor of the treatment group.
There was also a significant difference in primary endpoint rate in the pre-COVID-19 analysis between the treatment and control groups (0.553 vs 0.682 per patient-year); this difference “almost disappeared” during COVID-19 with a 21% decrease in the control group relative to the pre-COVID-19 analysis.
Overall incidence of investigator-reported adverse events (AEs), serious AEs, and AEs leading to study discontinuation were similar across both groups in both analyses.
Study limitations include patient masking to their treatment assignment, the 12-month follow-up duration, and the impact of COVID-19 on data collection.
“Hemodynamic-guided management across the spectrum of ejection fraction and symptom severity was safe but did not reduce a composite of mortality and total heart failure events,” the researchers wrote. “However, in a pre-COVID-19 impact analysis, a benefit of hemodynamic-guided management on the primary outcome…was shown.”
“These data affirm and expand the evidence base supporting the benefits of hemodynamic-guided management in patients with chronic heart failure and suggest that such an intervention might be applicable to a broader range of patients, including those with mild to moderate heart failure and those with elevated natriuretic peptides and no previous heart failure hospitalizations,” they concluded.
Disclosure: This clinical trial was supported by Abbott. Please see the original reference for a full list of authors’ disclosures.
Lindenfeld J, Zile MR, Desai AS, et al. Haemodynamic-guided management of heart failure (GUIDE-HF): a randomized controlled trial. Lancet. Published online August 27, 2021. doi:10.1016/S0140-6736(21)01754-2