https://www.healio.com/news/cardiology/20240320/device-to-treat-acute-decompensated-heart-failure-feasible-safe-in-firstinhuman-study

Key takeaways:

Device-based thoracic duct decompression reduced congestion safely in patients with acute decompensated heart failure.
The device targets congestion from the interstitial space, which diuretics mostly do not.

Among patients with acute decompensated heart failure, device-based thoracic duct decompression demonstrated the ability to reduce congestion safely, according to results of a first-in-human study.

“We have made little or no progress over the past several decades, frankly since the advent of diuretic therapies, to treat acute decompensated heart failure (ADHF),” William T. Abraham, MD, FACP, FACC, FAHA, FESC, FRCPE, professor of medicine, physiology and cell biology and a College of Medicine Distinguished Professor in the division of cardiovascular medicine at The Ohio State University Wexner Medical Center, told Healio. “We have seen many failed trials evaluating the pharmacological treatment of ADHF. This has created a large unmet need and set the stage for device development for the treatment of ADHF.”

Abraham presented 30-day, 90-day and 6-month results from the first nine patients of the DELTA-HF trial of thoracic duct decompression with a novel catheter-based system (eLym, WhiteSwell) on top of IV loop diuretics, as well as some early effectiveness data, at the Technology and Heart Failure Therapeutics (THT) annual meeting.

“When I first heard about the concept behind the development of this device, it was one of those ‘lightbulb going off’ moments,” Abraham told Healio. “This device targets the interstitial space for decongestion, resulting in simultaneous or concurrent emptying of the interstitial and intravascular spaces using the WhiteSwell eLym system along with diuretic therapy, with the goal of more adequately and efficiently decongesting the patient. The ‘lightbulb moment’ was appreciating that in decompensated heart failure, as in health, most of the fluid resides in the interstitial space. Very little of the volume expansion in heart failure is in the intravascular space. Yet diuretic therapy alone only passively addresses the interstitial fluid. The goal of the eLym system is to deliver a therapy called thoracic duct decompression for interstitial decongestion. That means lowering the local intravascular venous pressure around the region in which the thoracic duct empties into the venous circulation, and that’s at the left venous angle. In doing so, it restores a normal pressure gradient between the thoracic duct and the venous circulation and allows better emptying of lymphatic fluid into the venous circulation, where it then can be removed from the body via the kidneys using standard diuretic therapy.”

Among the first nine patients in the DELTA-HF trial, the mean age was 66 years and 67% were men. The technical success rate was 100% in terms of deployment, activation and removal of the eLym system.

In eight patients, there were no serious adverse events. The ninth “developed transient hypotension, which was treated with short-term use of dobutamine without any sequelae,” Abraham told Healio.

Mean weight loss between baseline and discharge was –5.9 kg, whereas level of daily diuretic use during the procedure was no different from outpatient levels (outpatient, 131 mg; procedure, 125 mg), Abraham said during the presentation.

Kidney function remained stable during and after the procedure, Abraham told Healio. At baseline, mean creatinine was 1.14 mg/dL, at the end of treatment and at discharge, it was 1.11 mg/dL, and at 30 days it was 1.13 mg/dL, he said.

Congestion was reduced based on peripheral edema-based assessment (peripheral edema scale score of more than 2 at baseline and 0 at 30 days) and orthopnea-based assessment (all patients with at least two-pillow orthopnea at baseline, but no orthopnea in any patient at discharge and 30 days), he said.

“And then using a congestion biomarker called Ca125, we demonstrated intermediate-term reductions in congestion that were sustained through 30 to 90 days, indicative of more complete decongestion,” Abraham told Healio.

In the 6 months before the procedure, the event rate of HF hospitalization or death was 1.4 per patient, whereas in the 6 months after the procedure, the rate was 0.3 per patient, a 77% reduction, demonstrating the potential of this approach for improving ADHF outcomes, Abraham said.

“The next steps here are to continue to enroll patients into this study, which is ongoing, and to gather additional initial feasibility, safety and effectiveness data,” Abraham told Healio. “Once that study is complete, if the additional enrollment confirms these current observations, we hope to move to the next big step, into a randomized trial.”

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GALWAY, Ireland – 7 October 2023 – WhiteSwell, a company pioneering a new paradigm in the treatment of acute decompensated heart failure (ADHF), announced today positive initial results from its ongoing DELTA-HF trial evaluating the WhiteSwell eLym™ System. The data were presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2023 in Cleveland, Ohio.  

In DELTA-HF, a minimally invasive catheter-based system is introduced to facilitate the removal of excess fluid from the body’s tissues and organs concurrent with diuretic removal of excess vascular fluid. The eLym System targets the body’s largest lymphatic vessel and creates pressure conditions that support the tissue drainage capabilities of the overwhelmed lymphatic system.  

Nine hospitalized patients received eLym therapy in conjunction with diuretic therapy, while six patients received standard of care treatment with loop diuretics alone.   

Summary of key findings:

• Treatment with the eLym System was performed safely and successfully.
  • Deployed and activated in nine patients with a mean treatment time of 24 hours.
  • No patient experienced a serious procedure-, device-, or therapy-related adverse event.
• Early clinical results are promising and support further clinical investigation.
  • Patients who underwent therapy with the eLym System plus loop diuretic lost a mean of 6.0±4.6 kg from baseline to hospital discharge while maintaining kidney function, as measured by a stable or improved creatinine (mean Δ -0.10±0.12 mg/dL).
  • The loop diuretic-only group lost a mean of 3.3±3.7 kg.
  • One treated patient (1/9, 11%) was hospitalized within 30 days of discharge.  

“It cannot be overemphasized how significant and challenging it is to fully decongest patients hospitalized with decompensated heart failure. Patients with persistent congestion at discharge are more likely to be rehospitalized, are less likely to be treated with optimal medical therapy and are at greater risk of poor outcomes. Most of the fluid accumulates in the tissues, and we have not previously had a way to actively target that fluid,” said William Abraham, M.D., Professor of Medicine, Physiology, and Cell Biology at The Ohio State University Wexner Medical Center. “WhiteSwell’s ingenious approach of reducing thoracic duct pressure to facilitate lymphatic drainage of the tissues enables us to actively address both interstitial tissue and intravascular decongestion simultaneously. I’m particularly encouraged by the amount of decongestion achieved with stable or improved creatinine, an indicator of kidney function.”

“This is a new approach, and we are excited to investigate WhiteSwell’s catheter-based system,” said Zviad Kereselidze, M.D., Head of the ICCU at Tbilisi Heart Center. “We have treated some of our most challenging patients who are frequently hospitalized with congestion, and we have been pleasantly surprised with how well they have decongested at the time of discharge and how the benefit was sustained at 30-day follow-up.”

WhiteSwell continues to evaluate this unique approach to treating ADHF patients with continued enrollment and follow-up in The Safety and Feasibility of the eLym™ System for the Decongestion of Excess Lymphatic Fluid via the Thoracic Duct in Acute Decompensated Heart Failure (DELTA-HF) Trial. The company looks forward to sharing additional data in the future.   

About the DELTA-HF Trial

The DELTA-HF trial is a non-randomized early feasibility trial evaluating the safety and performance of the eLym System in the treatment of fluid overload or congestion in patients with ADHF. 

About the eLym™ System

The eLym System is a minimally invasive catheter-based system designed to facilitate the removal of excess fluid from tissues and organs (interstitial fluid) in patients with ADHF by supporting the overwhelmed lymphatic system’s ability to actively drain fluid. The eLym System is deployed in the left internal jugular and innominate veins near where the lymphatic system’s major highway, the thoracic duct, connects. It creates a low-pressure zone to facilitate fluid drainage in conjunction with intravenous diuretics.

About Acute Decompensated Heart Failure (ADHF)

ADHF is an episode of worsening heart failure symptoms that results in millions of hospitalizations worldwide each year, including three million in the U.S. alone.¹ Patients with ADHF experience difficulty breathing, fatigue, and edema (swelling) due to fluid back-up in the lungs and other parts of the body (congestion). The condition requires hospital-based treatment to remove excess fluid in a process called decongestion. Complete decongestion is the goal of ADHF treatment since residual congestion at hospital discharge is the strongest predictor of rehospitalization and death.2 As many as half of ADHF patients are discharged from the hospital not fully decongested, and one out of four ADHF patients is readmitted to the hospital within one month.^3,4,5

About the Lymphatic System and ADHF

In healthy individuals, the lymphatic system continuously captures fluid from tissues throughout the body and pumps it back into the vascular system to maintain homeostasis. In ADHF, excess fluid collects in the tissues of the body (the interstitial compartment), causing edema and an increase in venous blood pressure. Excess tissue fluid and high venous blood pressure interfere with the lymphatic system’s ability to move fluid back to the vascular system, which can further exacerbate congestion.

About WhiteSwell

WhiteSwell is a patient-focused company dedicated to improving treatment of acute decompensated heart failure (ADHF), a primary cause of repeat hospitalization and emergency room visits. A privately held company, WhiteSwell is headquartered in Galway, Ireland.  For more information, visit www.whiteswell.com.

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1. Hollenberg et al., J Am Coll Cardiol 2019;74:1966–2011.   (1M annual hospital discharges with HF as primary diagnosis and 2M hospital discharges with HF as secondary contributing diagnosis.)  
2. Martens & Mullens, How to tackle congestion in acute heart failure, Korean J Intern Med 2018;33:462-473
3. Girerd et al, Integrative Assessment of Congestion in Heart Failure Throughout the Patient Journey, J Am Coll Cardiol HF 2018;6:273–85
4.  Arrigo et al, Nature Reviews Disease Primers volume 6, Article number: 16 (2020) 
5.  Rubio-Gracia, J. et al. (2018). International Journal of Cardiology, 258, pp. 185-191. 

GALWAY, Ireland – December 11, 2018 – WhiteSwell, a company pioneering new ways to treat acute decompensated heart failure, today announced the close of a $30 million series B funding round led by RA Capital Management and an InCube Ventures syndicate, with participation from other investors. Funds from the round will be used to support product development and a pivotal study of the company’s innovative technology for the treatment of acute decompensated heart failure (ADHF).

The company also announced that WhiteSwell founder and chief technology officer Yaacov Nitzan has been joined by chief executive officer Eamon Brady and chief financial officer Seán Mac Réamoinn, who formerly served as chief executive officer and chief financial officer of Neuravi, a stroke treatment company acquired by Johnson & Johnson last year.

“WhiteSwell was founded on insights that arose from our team’s research on the complex fluid dynamics of heart failure patients, leading to the company’s innovative leap in treatment strategy,” said Brady. “This financing is an important milestone that will enable us to tackle an enormous clinical problem that affects millions of families.”

ADHF is an episode of worsening heart failure symptoms that results in millions of hospitalizations worldwide each year, including nearly two million in the U.S. alone.¹ Patients with ADHF experience difficulty breathing, fatigue, and edema (swelling) due to fluid back-up in the lungs and other parts of the body (congestion). The condition requires immediate treatment to remove excess fluid in a process called decongestion. Complete decongestion is the goal of ADHF treatment, as residual congestion at hospital discharge is the strongest predictor of rehospitalization and death.^2,3,4 As many as half of ADHF patients are discharged from the hospital not fully decongested,⁵ and 25% of ADHF patients are readmitted to the hospital within one month.^6,7,8

“I am excited about the potential for WhiteSwell’s therapy to accomplish complete decongestion with preservation of renal function, which is considered the holy grail of ADHF treatment,” said William Abraham, M.D., director, division of Cardiovascular Medicine at The Ohio State University in Columbus, Ohio. “I was immediately intrigued by WhiteSwell’s ingenuity in targeting the lymphatic system, which plays a major role in fluid management, moving interstitial fluid into the vascular system.”

Complete decongestion is difficult to achieve with current ADHF treatments, which focus on removal of excess fluid from the vascular system. WhiteSwell is taking a different approach, targeting removal of excess fluid in the interstitial system, the fluid-filled spaces in connective tissue all over the body that are outside of the vascular system. The company’s innovative technology enhances the natural fluid removal process of the lymphatic system, a network of vessels that permeates the interstitial system to drain excess fluid into the vascular system to achieve interstitial decongestion. Currently there is no effective treatment to directly remove excess fluid from lung and other interstitial tissues.

“WhiteSwell’s mission is aligned with our goal of helping to advance more cost-effective and impactful healthcare outcomes,” said Andrew Levin, M.D., Ph.D., Managing Director at RA Capital. “We are excited about the game-changing potential of WhiteSwell’s technology to benefit patients with ADHF and reduce costs.”

“We’re looking forward to working with WhiteSwell’s experienced leadership team to deliver a compelling new therapy for ADHF, and we see the potential for it to become a blockbuster medtech product,” said Andrew Farquharson, Managing Director and Co-founder of InCube Ventures. “The WhiteSwell approach is disruptive therapy in an area that has experienced relatively little innovation in the past few decades.”

WhiteSwell is currently conducting an early feasibility study at clinical sites in the U.S., Israel and Europe.

About the Lymphatic System and ADHF

In healthy individuals, the lymphatic system continuously captures fluid from tissues throughout the body and pumps it back into the vascular system to maintain homeostasis. In ADHF patients, the heart does not pump effectively, excess fluid collects in the tissues of the body (the interstitial system) and blood pressure rises. Excess tissue fluid and high blood pressure interfere with the natural fluid removal process of the lymphatic system, which can further exacerbate congestion.

About WhiteSwell

WhiteSwell is a science-driven company dedicated to improving treatment of acute decompensated heart failure (ADHF), a primary cause of repeat hospitalization and emergency room visits. Founded by chief technology officer Yaacov Nitzan in 2014, the company is pioneering a minimally invasive catheter-based approach designed to more efficiently remove excess interstitial fluid in patients with ADHF by enhancing the natural fluid removal process of the lymphatic system. For more information visit www.whiteswell.com.

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