Doppler-Based Renal Venous Stasis Index as a New Prognostic Marker in Right Heart Failure

Abstract

Background: Persistent congestion with deteriorating renal function is an important cause of adverse outcomes in heart failure. Renal Doppler ultrasonography has been proposed to assess renal congestion but is not fully characterized, and current approaches do not reflect the full continuum of renal congestion. We aimed to characterize new approaches to evaluate renal congestion using Doppler ultrasonography. Methods: We enrolled 205 patients with suspected or pre-diagnosed pulmonary hypertension (PH) undergoing right heart catheterization. PH is the most common precursor to right ventricular failure, and thus represents an ideal scenario to study congestion. Patients underwent renal Doppler ultrasonography and assessment of invasive cardiopulmonary haemodynamics, echocardiography, renal function, intra-abdominal pressure, and hormonal and hydration status. Four renal venous flow patterns (RVFPs) and a novel renal venous stasis index (RVSI) were defined. The rate of PH-related morbidity and all-cause mortality (composite endpoint) was evaluated for 1 year post-discharge. Associations with outcome were assessed using Cox proportional hazard models. Prognostic utility of RVSI and RVFP was compared using receiver operating characteristic (ROC) curves. Findings: RVSI increased across the RVFPs (p<0*0001), and was significantly associated with right heart and renal function, intra-abdominal pressure, and hormonal and hydration status. During follow-up, the morbidity/mortality endpoint occurred in 91 patients and was independently predicted by RVSI (RVSI in 3rd tertile vs RVSI=0: hazard ratio 4*72 [95% confidence interval 2*10-10*59; p<0*0001]). ROC curves suggested superiority of RVSI to RVFPs in predicting outcome (area under curve: 0*789 and 0*761, respectively). Interpretation: We describe four RVFPs, and we propose RVSI as a conceptually new, non-invasive, objective, and reproducible Doppler index of renal congestion. RVSI might provide additional information to stratify vulnerable patients with right heart failure. Clinical Trial Number: The study is registered at www.ClinicalTrials.gov (NCT03039959). Funding: This study was funded by the German Research Foundation (DFG) SFB1213, projects B08 and B07. Declaration of Interests: Dr. Seeger disclosed personal fees for consulting from Bayer Pharma AG, from Liquidia Technologies, Inc, and from United Therapeutics Corporation outside the submitted work. Dr. Gall discloses personal fees and non-financial support from Actelion, AstraZeneca, Bayer, BMS, GlaxoSmithKline, Janssen Cilag, Lilly, MSD, Novartis, Pfizer, and United Therapeutics/OMT outside the submitted work. Dr. Gofrani discloses grants from German Research Foundation (DFG) during the conduct of the study, and personal fees from Actelion, Bayer, GSK, Novartis, Pfizer, Bellerophon Pulse Technologies, and MSD Merck Sharpe & Dohme outside the submitted work. None of the other authors declare any competing interests. Ethical Approval Statement: The study was approved by the local Human Research Ethics Committee (AZ 237/16) and complied with the Declaration of Helsinki. All participants gave signed informed consent and were included in the Giessen PH registry.