Key Points:
- Pulmonary congestion is a major driver of heart failure hospitalizations and often proceed clinical symptoms by days to weeks.
- The IMPEDANCE-HFpEF trial randomized 150 HFpEF patients 1:1 to lung impedance (LI)-guided diuretic therapy or standard care, using the CardioSet device to directly measure pulmonary congestion over a mean follow-up of 38.4 months.
- LI-guided therapy resulted in an 81% reduction in heart failure hospitalizations and a 65% reduction in all-cause mortality, with the benefit driven by earlier intervention rather than diuretic treatment intensity.
Patients with heart failure with preserved ejection fraction (HFpEF) are often marred by significant morbidity with recurrent hospitalizations. A critical limitation of current practice is the inability to directly and accurately measure fluid accumulations, particularly pulmonary congestion which often proceeds clinical symptoms or hospitalizations by up to weeks. Existing impedance-based tools for objectively measuring pulmonary congestion have been hampered by interference from the chest wall. A novel, non-invasive tool, the CardioSet device, overcomes this limitation using a multi-electrode configuration that isolates and removes the chest wall signal which enables actionable measurements even when fluid changes are small.
The IMPEDANCE-HFpEF trial was a single-blind, single-center randomized controlled trial conducted at Hillel Yaffe Medical Center in Israel (NCT02661841). The study enrolled 150 patients with HFpEF, defined by LVEF >50%, NYHA class I–IV symptoms, a prior HF hospitalization or emergency department visit within the preceding year, and elevated NT-proBNP. Patients were randomized 1:1 to LI-guided therapy or standard care, with monthly outpatient HF clinic visits in both arms. In the LI-guided group, treating physicians had access to lung impedance measurements obtained using the CardioSet device and adjusted diuretic therapy according to a predefined protocol based on the lung impedance ratio (LIR) — a calculated index of pulmonary congestion relative to each patient’s predicted normal lung impedance. The primary endpoint was recurrent HF hospitalization. Mean follow-up was 38.4 ± 22.8 months.
The average age was approximately 75 years and over 60% of participants were female. Baseline characteristics were well matched between groups. LI-guided therapy produced an 81% reduction in heart failure (HR 0.19, p<0.01 at 7 years). The time to first HF hospitalization was substantially longer in the LI-guided group (602 vs. 83 days, p<0.01). Secondary analysis of all-cause mortality showed reduction by 65% (HR 0.35, p<0.01 at 7 years). The benefit of the LI-group was driven by the timing of diuretic adjustments rather than their intensity: LI-guided therapy triggered up-titration earlier in the course of congestion as measured by the LIR (median LIR −20.8% vs. −35.4% in controls, p<0.01), while the efficacy of diuretic adjustments once made was similar in both groups. LI-guided patients also spent nearly twice as much time in the therapeutic LIR range (median 96.6% vs. 50.0%, p<0.01). No device-related adverse events were reported. Limitations of the trial include its single-center design, which limits generalizability, and the single-blind nature of the study.
Lead investigator Dr. Michael Kleiner-Shochat concluded that “this device offers a way to change the treatment of patients with heart failure in order to start treatment early — before the patient starts to experience symptoms. The secret of success is to enable us to intervene at the preclinical stage.” He described the device as “a simple, scalable device that could be used at each point of care — in clinics and, in the future, in the patient’s home.” These results suggest that direct monitoring of pulmonary congestion may play a critical role in the future management of HFpEF.