Quantifying interstitial and intravascular congestion by ultrasound in patients with heart failure following temporary suspension of diuretics (QUEST-HF)

Background

Symptoms and signs of heart failure (HF), and prognosis, are worsened by congestion. Identifying congestion at earlier stages might allow for timely interventions, leading to delays in progression of HF, improved well-being and clinical outcomes.

Purpose

To assess the feasibility of using ultrasound (US) to identify and quantify changes in interstitial and intravascular congestion, following temporary suspension of diuretics in patients with HF.

Methods

This is an open-label, randomised cross-over trial, comprising two 48-hour study investigation periods, separated by an interval of at least one week. We enrolled consenting adults with a clinical diagnosis of HF, on guideline-recommended HF therapy including a loop diuretic, whose NT-proBNP was >125ng/L. Key exclusion criteria were atrial fibrillation (AF), estimated glomerular filtration rate (eGFR) <30ml/min/1.73m2, significant valve disease, or a likelihood of poor tolerability of a 48-hour omission of diuretics.

Patients were randomised to the order in which their existing prescribed loop diuretics and mineralocorticoid receptor antagonist (MRA), if taking one, would be either omitted for 48 hours prior to the study visit, or taken as usual over this period. On the morning of each study visit, participants were asked to omit that morning dose. During each study visit, after clinical evaluation, participants had blood samples taken, an echocardiogram, and ultrasonographic assessment of lung, renal and inferior vena cava and internal jugular congestion. All ultrasound images were analysed by the same cardiologist, who was blinded to the order of the study visits, clinical and laboratory findings.

Results

We enrolled 20 patients (median age 72 (65-77) years, median NT-proBNP 343 (239-618) ng/L, median left ventricular ejection fraction (LVEF) 45 (40-50)%). Omission of diuretics for 48 hours led to increases in left ventricular end diastolic volume (LVEDV; 8.4ml, 0.8 to 16.0ml, p=0.03), left ventricular end systolic volume (LVESV; 5.7ml, 1.0 to 10.4ml, p=0.02) and max left atrial volume (LAV), (4.9ml, 0.5 to 9.2ml, p=0.03). There were no significant changes in NT-proBNP (33ng/L, 105 to171ng/L, p=0.6), LVEF or ultrasound markers of congestion. No changes were observed on blood pressure, body weight or renal function.

Conclusion

A 48-hour suspension of diuretics increases left ventricular and atrial volumes in patients with HF, that can be identified by ultrasound. How these findings may be used to guide clinical practice requires further study.