Multi-organ sonographic assessment of congestion has incremental prognostic value in outpatients with heart failure irrespective of left ventricular ejection fraction
Authors: Pugliese N R , Pellicori P , Filidei F , Del Punta L , De Biase N , Balletti A , Di Fiore V , Mengozzi A , Taddei S , Gargani L , Mullens W , Cleland J G F , Masi S 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Congestion is a key driver of symptoms, disease progression and prognosis for patients with heart failure (HF), irrespective of left ventricular ejection fraction (LVEF). However, clinically overt congestion is often undiagnosed unless severe. Recent research has shown that ultrasonographic quantification of systemic venous (i.e. inferior vena cava), renal venous and lung (B-lines) congestion is feasible and identifies HF patients with a worse prognosis.

Purpose
Whether a simultaneous multi-organ evaluation of congestion by ultrasound may improve risk stratification in HF is unknown. In the present study, we assessed signs of ultrasonographic congestion in the inferior vena cava, lungs and kidneys in HF patients across the LVEF spectrum and investigated their association with pathophysiology, clinical characteristics and prognosis.

Methods
We prospectively enrolled 326 patients with a prior clinical diagnosis of HF attending a routine follow-up visit. We also enrolled 102 consecutive patients with cardiovascular risk factors (including hypertension, type II diabetes mellitus or chronic ischaemic heart disease) and no history of HF; these latter patients had NT-proBNP levels &lt;125 ng/L, LVEF &gt;50%, and were not taking loop diuretics. All patients underwent a complete clinical assessment, blood and urine tests, and an ultrasound evaluation. Ultrasound congestion was defined as inferior vena cava ≥21 mm, highest tertile of lung B-lines or discontinuous renal venous flow.

Results
The final population consisted of 310 HF patients (median age 77 years, median NT-proBNP 1037 ng/L, 51% with LVEF &lt;50%), and 101 subjects without HF. Among the 224 HF patients (72%) with no clinical signs of congestion, 95 (42%) had at least one sign of congestion by ultrasound (p&lt;0.0001). HF patients with ≥2 ultrasound signs were older, had greater neurohormonal activation (i.e., higher NT-proBNP; Figure 1), lower urinary sodium concentration, and larger left atria despite similar LVEF. During a median follow-up of 13 (interquartile range 6–15) months, 77 HF patients (19%) died or were hospitalized for HF. HF patients without ultrasonographic evidence of congestion had a similar outcome to subjects without HF (reference; HR 1.02, 95% CI 0.86 – 1.35), while those with ≥2 ultrasound signs had the worst outcome (HR 26.7, 95% CI 12.4–63.6), even after adjusting for multiple clinical variables and NT-proBNP (Figure 2). Adding multi-organ assessment of congestion by ultrasound to a clinical model, including NT-proBNP, provided a 28% net reclassification improvement (p=0.03).

Conclusion
Simultaneous assessment of pulmonary, systemic venous and kidney congestion by ultrasound identifies a high prevalence of sub-clinical congestion associated with poor outcomes in HF, irrespective of LVEF. The speed of investigation, along with the widespread availability and relatively low cost of ultrasound, makes this protocol easy to implement for real-time assessment of congestion.