Cartridge and method for increasing myocardial function
Inventors
Humes, H. David • Buffington, Deborah A.
Assignees
Innovative Biotherapies Inc • Seastar Medical Inc
Publication Number
US-11439739-B2
Publication Date
2022-09-13
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 addresses the treatment and prevention of inflammatory myocardial conditions by providing methods and a cytopheretic cartridge that extracorporeally sequesters and reduces the inflammatory activity of specific cell types, such as activated leukocytes and platelets, from a subject’s body fluid. The core of the invention is the use of a cartridge comprising a rigid housing with an inner volume, fluid inlet and outlet ports, and a solid support with a fluid-contacting surface capable of sequestering these activated cells. As blood passes through the cartridge, activated leukocytes and/or platelets are sequestered on the surface, and their pro-inflammatory action is inhibited or deactivated, directly leading to increased myocardial function.
Chronic heart failure (CHF) and acute decompensated heart failure (ADHF) are conditions characterized by abnormal or excessive chronic activation of the immune system, significantly contributing to life-threatening myocardial dysfunction. Current therapeutic strategies, including pharmacologic agents and mechanical devices, have been largely unsuccessful in improving clinical outcomes. Therefore, there is an unmet need for improved treatments targeting the inflammatory basis of myocardial dysfunction, which this invention seeks to address by directly extracting and treating inflammatory cells from circulation.
The methods disclosed include introducing blood from a subject into the cartridge to sequester cells, then treating those sequestered cells with agents—such as calcium chelators like citrate, or other leukocyte inhibiting agents—to inhibit the release of pro-inflammatory substances or deactivate the cells. The result is a measurable increase in specific myocardial function parameters, such as left ventricular ejection fraction and cardiac output, that can be maintained following treatment. Various embodiments specify detailed cartridge parameters, including surface area/inner volume (SA/IV) ratios and suitable flow rates, to adapt the therapy for different patient populations and clinical needs.
Claims Coverage
The patent claims cover five main inventive features related to methods and devices for increasing myocardial function and treating inflammatory myocardial conditions using selective cytopheresis cartridges and specific treatment protocols.
Method of increasing myocardial function in chronic heart failure by extracorporeal sequestration and treatment of leukocytes/platelets
The method comprises: - Extracorporeally sequestering activated leukocytes and/or activated platelets present in blood from the subject using a cartridge having a rigid housing (defining an inner volume, fluid inlet port, and outlet port) and a solid support with a fluid-contacting surface capable of sequestering activated leukocytes/platelets. - Introducing the blood into the cartridge under conditions that permit sequestration on the solid support. - Treating the sequestered leukocytes and/or platelets to inhibit release of a pro-inflammatory substance or to deactivate the cells, thereby increasing myocardial function (including parameters such as left ventricular ejection fraction, cardiac output, systemic vascular resistance, etc.) compared to pre-treatment.
Cartridge design with defined SA/IV ratio and solid support for cell sequestration
The cartridge features: - A rigid housing defining an inner volume, fluid inlet port, and fluid outlet port, with the inner volume in flow communication with both ports. - A solid support (fiber or membrane) within the housing, defining a fluid-contacting surface capable of sequestering activated leukocytes and/or activated platelets. - The cartridge may have an SA/IV (surface area to inner volume) ratio in specified ranges (e.g., greater than 25 cm⁻¹, 25 cm⁻¹ to 2,000 cm⁻¹, or not greater than 80 cm⁻¹) and a packing density of the solid support ranging from 20% to 65%.
Treatment of sequestered cells with specific agents to inhibit inflammation
After sequestration, the leukocytes and/or platelets are treated with: - A calcium chelating agent such as citrate, sodium hexametaphosphate, ethylene diamine tetra-acetic acid (EDTA), or others. - Alternative agents like immunosuppressants, serine leukocyte inhibitors, nitric oxide, polymorphonuclear leukocyte inhibitor factor, or secretory leukocyte inhibitors. - The agents can be introduced into the blood prior to, during, or after the sequestration step, and the treatment is sustained over defined periods (e.g., 2–48 hours, at least 2–12 hours, etc.).
Methods for treating inflammatory conditions including chronic heart failure using specified cartridges
- Providing a cartridge comprising a rigid housing, fluid inlet and outlet ports, and a fluid permeable solid support defining a fluid-contacting surface capable of sequestering activated leukocytes and/or platelets, with a specified SA/IV ratio (e.g., not greater than 80 cm⁻¹). - Introducing blood from the subject into the cartridge under conditions permitting sequestration of the activated cells. - Optionally, treating the sequestered cells with a calcium chelator or other agent to reduce the risk of developing or to alleviate inflammation. - The method can further include returning the processed cells to the subject.
Maintaining improved myocardial function and treatment timing
- The inventive features specify that increased myocardial function after treatment (as measured by parameters like ejection fraction or cardiac output) can be maintained for specified periods (at least 6 or 24 hours after treatment ends). - The methods cover timing of treatment, including durations for exposing leukocytes/platelets to the treating agent (ranging from at least 2 hours to up to 48 hours), and specify returning the treated blood to the subject.
The inventive features establish a comprehensive method and device for extracorporeally sequestering and treating activated leukocytes and/or platelets in subjects with inflammatory myocardial conditions using tailored cartridges and agents, resulting in improved, sustained myocardial function.
Stated Advantages
The invention provides improved methods for treating inflammatory conditions affecting myocardial function, particularly where existing drug therapies have failed.
The selective sequestration and deactivation of activated leukocytes and platelets lead to measurable improvements in myocardial function, such as increased left ventricular ejection fraction and cardiac output.
Treatment with the disclosed cartridge and agents can rapidly and sustainably increase cardiac function parameters in subjects with chronic heart failure or acute decompensated heart failure.
The use of a cartridge with a defined surface area-to-volume ratio allows for tailored treatment to different patient sizes and clinical needs, minimizing the risk of complications like leukopenia or thrombocytopenia.
The combined use of the cartridge and calcium chelating agent, such as citrate, demonstrated improved cardiovascular performance and fluid removal not attainable with conventional therapies.
Documented Applications
Treating and/or preventing inflammatory myocardial conditions, including chronic heart failure (CHF) and acute decompensated heart failure (ADHF).
Therapeutic or prophylactic increase of myocardial function in subjects experiencing myocardial dysfunction secondary to inflammatory cell penetration of heart tissue.
Treating or preventing organ/tissue rejection following transplantation of an organ (such as heart, liver, or kidney) or tissue.
Use in pediatric and adult subjects, with cartridge configurations adapted to patient age and body weight.
Use of the device in acute systemic inflammatory conditions, such as sepsis and systemic inflammatory response syndrome (SIRS), as demonstrated in animal models.
Integration of the cartridge into extracorporeal blood circuits, including those used in chronic dialysis, hemofiltration, and cardiopulmonary bypass surgery.
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