Claudia Brigato (1), Gabriele Cusumano (2), Rosa Cascone (2), Francesco Giovagnoli (1), Andrea D'Amato (3), Camilla Segato (3), Paolo Severino (3), Antonietta Gigante (1)

(1) Department of Translational and Precision Medicine, University of Rome "La Sapienza"
(2) Department of Translational and Precision Medicine, University of Rome "La Sapienza".
(3) Department of Clinical, Internal Medicine, Anesthesiological and Cardiovascular Sciences, University of Rome "La Sapienza"

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Background: Heart failure with reduced ejection fraction (HFrEF) is a clinical syndrome characterized by systemic congestion, which is a key target in therapeutic management. In HFrEF renal venous congestion due to backward heart failure leads to disturbance of renal function. Increased pressure in the right atrium and central veins is transmitted to the renal veins, causing congestion and decreased the glomerular filtration rate (GFR). Recent studies have shown that ultrasound can perform a complementary assessment to the clinic to better quantify the degree of congestion. The Venous Excess Ultrasound (VExUS) system is a novel ultrasound protocol that combines venous Doppler assessments of multiple districts, including the inferior vena cava, internal jugular vein, lungs, hepatic and kidneys veins.

Aim: The aim of this study is to assess renal venous congestion in outpatients with HFrEF, with particular focus on identifying subclinical congestion through the VExUS grading system and the correlation between clinical, ultrasound and laboratory findings.

Methods: We conducted a prospective observational study with the current enrollment of 35 outpatients (6 female) with HFrEF with a median age of 75 (56-89). The patients underwent multiple clinical diagnostic tests (NYHA class, edema, crackles), laboratory tests (including NT-proBNP, creatininemia with calculation of eGFR according to CKD-EPI), ultrasound tests such VExUS system [ internal jugular vein diameter ratio (iJVD ratio) ,inferio vena cava(IVC), B lines, renal and hepatic venous flow). The iJVD ratio is given by the ratio between the diameter after the Valsalva maneuver and at rest, measured with the patient in a semi-supine position, with the head and neck elevated at approximately 45 degrees using high-frequency linear transducer. Hepatic and interlobar renal veins can be identifed by positioning a convex transducer to perform Doppler acquisition with the patient in supine position. A pathological renal flow is defined as biphasic or pulsatile, Lung congestion is defined by the presence of at least three B-lines (in a specific intercostal space) in at least two zones per hemithorax. Assessment of the IVC was performed using subcostal longitudinal views applying M-mode convex transducer. Pathological IVC values were defined as diameter ≥ 2.1 cm and a respiratory collapsibility index of less than 50%. Descriptive statistics, chi-square tests, ANOVA, and non-parametric correlation analyses (Spearman and Mann-Whitney U) were performed with Jamovi version 2.6.26.0.

Results: At the time of enrollment, all patients already on optimized heart failure therapy with SGLT2i, MRA, ARNI/ACEi, and beta-blocker underwent VExUS evaluation and had started therapy with Vericiguat.Median serum creatinine was 1,29 mg/dl (0,6-3,1), median eGFR 54 ml/min (18-98) and median NT-proBNP was 1542 pg/ml (97-8890). We found that 15 patients (42.9%) with a median age of 76 (62-87) had altered renal venous flow: 9 patients (60%) had a biphasic pattern and 6 patients (40%) had a pulsatile pattern. Clinically, 40% of patients had edema and 66% had crackles. The median creatinine value was 1.96 mg/dl (0.6-3,1 ), 11 patients (73%) had chronic kidney disease and the median NT-proBNP was 1824 pg/ml. All patients had a positive JVD Radio <4. Five patients had a dilated IVC ≥ 21 mm) and it was collapsible >50% in 4 patients. Pulmonary B-lines were present in 12 patients (80%) and 10 patients had altered hepatic venous flow. There is a significant correlation between renal venous congestion and NYHA functional class (p=0.013), as well as with creatinine values (p=0.027). Additionally, we found a significant correlation between renal venous congestion and the presence of crackles(p=0.036), but not with edema (p=0.383). The VExUS system also showed a significant correlation between renal venous congestion and altered hepatic venous flow (p=0.004) and pulmonary B-lines (p<0.001). Furthermore, we found a significant correlation between renal venous congestion and the diameter of the inferior vena cava (p<0.001), but not with its collapsibility.

Discussion: The high prevalence of altered renal venous flow in our study population indicates that renal venous congestion is a significant issue in patients with HFrEF. This congestion is associated with increased creatinine values and higher NYHA functional class. The correlation between renal venous congestion and creatinine values warrants further evaluation to determine if it represents a functional response to chronic diuretic therapy, a manifestation of cardiorenal syndrome, or an indicator of systemic worsening. Furthermore, the association between renal venous congestion and NYHA functional class implies that renal venous congestion is likely an important determinant of functional capacity in patients with HFrEF.Conclusion: Renal venous congestion is a common finding in HFrEF, especially in patients with a significant degree of ultrasound congestion in other sites and it is associates with reduced renal function and poorer NYHA functional class.