Volume Removal in Heart Failure: Current Concepts and a Look into the Future

The Cardiorenal Medicine readership is well anointed to the challenges in delivery of care for the spectrum of cardiorenal patients. Thereby the journal platform is meant to drive interdisciplinary, well-rounded discussions among nephrologists, cardiologists, intensivists, and general internists on experimental and clinical studies for advancing clinical care. In this collection of papers in Cardiorenal Medicine, we have the honor of introducing a comprehensive discussion on the use of ultrafiltration strategies in the setting of heart failure and critical illness, medical, and device related. Accurately diagnosing volume overload, and subsequently applying the right therapeutic tool in the patients with heart failure is a complex task with variable success. We bring to you an exceptional grouping of contributions from experts in the field, discussing the latest advancements in fluid hemodynamic assessment, management strategies for fluid of overload and future novel directions for care of the cardiorenal patient.

There are a number of pathologies that contribute to fluid retention in heart failure such as inappropriate activation of the renin-angiotensin-aldosterone and of the sympathetic system. The clinical manifestations are varied and dependent on the adaptive cardiovascular responses which make the diagnosis and staging clinically challenging. Koratala et al. [1] provide us with a comprehensive review of different bedside tools and tests available for assessment of fluid status and fluid overload. They guide us through the use of different clinical signs, biomarkers, bioimpedance, and point-of-care ultrasound for the diagnosis and stratification of fluid overload. Although it is important to accurately diagnose the fluid status in patients with heart failure, management with diuretics remains a mainstay of clinical care. In this regard, Reis et al. [2] explore the various classes of diuretics and their combinations. The authors centered their attention on acute decompensated heart failure and diuretic resistance and then introduced the topic of extracorporeal fluid removal which is covered in later papers. One significant clinical dilemma that Reis et al. [2] introduce is the one of diuretic resistance and re-hospitalization risk. Kazory and Ronco explore this topic in depth [3]. In their review, authors detail state-of-the-art strategies for combination of diuretics to overcome inadequate diuretic responses and resistance.

The authors then reconvene to explore extracorporeal ultrafiltration [4] as a modality to be considered in the subset of patients with heart failure with treatment resistance fails combination diuretic approaches. In particular, they present the different clinical trials that examine extracorporeal ultrafiltration in a variety of clinical settings. Further, the manuscript highlights the need for future studies with newer technologies and a precision medicine approach. In this context, Murugan et al. [5] contribution explores specifically the key issue of ultrafiltration in the critical care setting. Significantly, the authors emphasize the principles for fluid management in the intensive care setting, and then they review the use of extracorporeal ultrafiltration, the rate of fluid removal given the hemodynamics (e.g., UF_net), and the available clinical trial data. Further, Murugan et al. also highlight the inconclusiveness of the available data for use of extracorporeal ultrafiltration but recognize the significant unmet clinical need given the relatively well accepted phenomenon of diuretic resistance. This is especially problematic for the increasing number of cardiorenal patients that do need extracorporeal ultrafiltration but not kidney replacement therapy. The authors call for alternative, innovative technologies that dissociate solute from volume management.

In response, Ronco et al. [6] present a white paper on the rationale for simpler and effective miniaturized bedside ultrafiltration devices. The lack of technical advances since the 1970s has slowed this field and the authors move beyond the scientific, technical real of existing modalities and presents the logistical, economic, and ethical considerations. There are a couple devices in early developmental stages like the wearable artificial kidney (International Renal Research Institute of Vicenza; IRRV) or the Artificial Diuresis-1 (AD 1; Medica S.p.A.; Medolla, Italy) developed to deliver slower ultrafiltration rates in the ambulatory setting or in the intensive care unit. Sgarabotto et al. [7] review the different technologies, the features that make them suitable for different clinical settings and the promise these advances in care are just a beginning to continue develop modalities for this unique population. The AD 1 is of particular interest given it wide applicability in home, ambulatory or in hospital settings. Lorenzin et al. [8] review their pioneering work on this device in culture, animal studies, and the clinical applicability. The authors present and report their findings in swine models on the hemodynamics, acid base status, and hematologic conditions during the ultrafiltration with the device. The findings from the swine model are the basis then for translatability to a first of its kind human pilot study with the device [9]. Reis et al. [9] present their rationale and design for a single-center, randomized, cross-over open-label pilot study on the AD 1 compared to traditional isolated ultrafiltration/extracorporeal ultrafiltration using a PrisMaX looking at safety outcomes. The authors have the trial registered with CESC Provincia di Vicenza_6.9.22(n.54/22)1575_29.9.22.

In summary, the collection of papers herein presented encompasses a thorough presentation of the spectrum of what is known for volume removal in the care of the cardiorenal patient. Authors in this collection of papers review the range of topics from the physiology of volume overload to traditional diuretic management for volume removal and on to extracorporeal ultrafiltration. What is unique about this collection is the collective expertise in reviewing this topic and the highlight of novel technologies.