Lung Impedance-Guided Therapy Reduces Hospitalizations in Heart Failure with Preserved Ejection Fraction: A Randomized Trial

BACKGROUND Prior studies demonstrated that lung impedance (LI)-guided therapy reduces heart failure (HF) hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS In this proof-of-concept, single-blind, single-center randomized controlled trial (NCT02661841), 150 HFpEF patients (NYHA class I-IV, LVEF >50%, elevated NT-proBNP, prior HF hospitalization) were randomized 1:1 to LI-guided management or usual care. LI was measured noninvasively at monthly outpatient visits using the FDA-approved CardioSet device. The primary endpoint was recurrent HF hospitalization. Mean follow-up was 38.4±22.8 months. HF hospitalizations were significantly reduced in the LI-guided group (HR 0.26; 95% CI 0.14-0.49; p<0.001; 20 vs 95 events). All-cause mortality (HR 0.40; 95% CI 0.18-0.87; p=0.02) and HF-specific mortality (HR 0.26; 95% CI 0.08-0.80; p=0.02) were also significantly lower. The Lung Impedance Ratio (LIR), reflecting each patient's degree of pulmonary congestion relative to their individual normal dry state, was used as a real-time fluid index to assess fluid status and guide diuretic titration at each visit. LI-guided patients spent significantly more time within the therapeutic LIR range, median 97% vs 49%; p<0.001, achieved through earlier treatment escalation (median LIR -20.8% vs -35.4%; p<0.01) and more conservative de-escalation (-13.7% vs -2.3%; p<0.01). Diuretic adjustment efficacy was similar between groups (LIR improvement +1.01% vs +1.36%; p=0.63), confirming benefit derived from precision timing rather than superior drug response. CONCLUSIONS In this proof-of-concept randomized trial, LI-guided management significantly reduced HF hospitalizations, all-cause mortality, and HF-specific mortality in HFpEF through precision timing of decongestion.