Cartridge and method for increasing myocardial function
Inventors
Humes, H. David • Buffington, Deborah A.
Assignees
Innovative Biotherapies Inc • Seastar Medical Inc
Publication Number
US-10722637-B2
Publication Date
2020-07-28
Expiration Date
2032-10-10
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Abstract
The present invention relates to a cytopheretic cartridge for use in treating and/or preventing inflammatory conditions that affect myocardial function and to related methods. The cartridge can be used in treating a subject with myocardial dysfunction, such as a subject with chronic heart failure and/or acute decompensated heart failure.
Core Innovation
The present invention provides a method and cytopheretic cartridge for treating and/or preventing inflammatory conditions that adversely affect myocardial function, particularly in subjects with chronic heart failure (CHF) or acute decompensated heart failure (ADHF). The method centers on the extracorporeal sequestration of activated leukocytes and/or platelets from blood using a cartridge that contains a rigid housing and a solid support with a fluid contacting surface capable of sequestering these activated cells from a subject's blood.
After sequestration, the sequestered leukocytes and/or platelets are treated in order to inhibit their release of pro-inflammatory substances or to deactivate the cells themselves. This can be achieved by exposing them to agents such as calcium chelating agents like citrate. The resultant effect is an increase in myocardial function, as assessed by parameters such as left ventricular ejection fraction, cardiac output, systemic vascular resistance, left ventricular stroke volume, and other cardiac function metrics.
The invention addresses the problem of myocardial dysfunction that arises from unwanted, persistent inflammation mediated by activated immune cells and platelets. Existing therapies for CHF and ADHF have shown limited efficacy, while the present method seeks to modulate or alleviate inflammation directly by removing or deactivating the inflammatory cells from circulation. This approach is designed to improve cardiac function and can be tailored through cartridge configuration to suit the needs of various patient populations, including those with organ transplants or those at risk for developing inflammatory myocardial conditions.
Claims Coverage
The patent includes several independent claims focused on methods for increasing myocardial function in subjects with acute decompensated heart failure through specific use of cytopheretic cartridges and associated treatments. There are three core inventive features described across the independent claims.
Extracorporeal sequestration and treatment of activated leukocytes and/or platelets using a cartridge to increase myocardial function
This inventive feature involves a method wherein blood from a subject with acute decompensated heart failure is extracorporeally processed in a cartridge comprising: - A rigid housing defining an inner volume (IV) with a fluid inlet port and a fluid outlet port, the inner volume being in fluid flow communication with both ports. - A solid support disposed within the housing, providing a fluid contacting surface with a surface area (SA) that sequesters activated leukocytes and/or platelets from the blood. - The blood is introduced into the cartridge under conditions enabling sequestration of the activated cells on the solid support’s fluid contacting surface. - Subsequently, the sequestered leukocytes and/or platelets are treated to inhibit release of pro-inflammatory substances or to deactivate said cells, thereby increasing myocardial function parameters such as left ventricular ejection fraction, cardiac output, systemic vascular resistance, left ventricular stroke volume, aortic pressure, left ventricular pressure, peak rate of change of left ventricular pressure during isovolumic contraction and relaxation, left ventricular end-diastolic pressure, myocardial oxygen consumption, and coronary flow reserve.
Generic method of extracorporeally sequestering and treating activated leukocytes and/or platelets to increase myocardial function
This inventive feature provides a method comprising: 1. Extracorporeally sequestering activated leukocytes and/or activated platelets present in blood from the subject. 2. Treating the sequestered leukocytes and/or platelets to inhibit release of a pro-inflammatory substance or to deactivate the cells, thereby increasing myocardial function relative to the subject’s pre-treatment state, as measured by established cardiac parameters. The method may involve treatment using a calcium chelating agent (including citrate) and specific cartridge configuration is optional but covered in dependent claims.
Sequestration of activated leukocytes and/or platelets via cartridge with plurality of fibers and subsequent treatment to increase myocardial function
This inventive feature further specifies the method by introducing blood into a cartridge that includes: - A rigid housing with an inner volume (IV), fluid inlet and outlet ports with flow communication. - A solid support comprising a plurality of fibers disposed within the housing, where the fibers provide a fluid contacting surface with sufficient area to sequester activated leukocytes and/or platelets as blood enters the housing. The claim encompasses cartridge parameters such as SA/IV ratio, packing density of fibers, fiber types (solid/hollow), and treatment with calcium chelating agents to achieve improved myocardial function.
The independent claims collectively protect methods for extracorporeal removal and deactivation of activated leukocytes and/or platelets using specifically configured cartridges to increase myocardial function in patients with acute decompensated heart failure, including variations involving treatment agents, cartridge composition, and operational parameters.
Stated Advantages
Improves myocardial function—such as left ventricular ejection fraction, cardiac output, systemic vascular resistance, and stroke volume—in subjects with chronic heart failure or acute decompensated heart failure.
Directly treats inflammation by extracorporeally removing and/or deactivating activated leukocytes and platelets, thereby overcoming limitations of drug-based therapies.
Can be tailored to various patient profiles by selecting cartridge design and operational parameters to balance efficacy and safety.
Increases cardiac output and contractility with sustained improvements maintained after cessation of therapy.
Reduces systemic inflammatory activity by inhibiting or deactivating pro-inflammatory cells, leading to improved survival and organ function (cardiac and renal) in preclinical models.
Documented Applications
Treating and/or preventing inflammatory conditions that affect myocardial function, specifically chronic heart failure (CHF) and acute decompensated heart failure (ADHF).
Increasing myocardial function in subjects experiencing myocardial dysfunction secondary to inflammatory cell penetration of heart tissue, including post-heart transplant patients.
Therapeutic and prophylactic treatment for subjects at risk of or experiencing organ/tissue rejection after transplantation.
Use during cardiopulmonary bypass surgery to disrupt the systemic leukocyte response and ameliorate systemic inflammatory response syndrome (SIRS).
Treatment of sepsis-associated inflammation and prevention of multi-organ dysfunction by extracorporeal cytopheresis of activated leukocytes.
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