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Cardiac Catheters for Delivery of Cell Suspensions

Cardiac Catheters for Delivery of Cell Suspensions. Donald Nick Jensen, DVM, MS Division of Cardiovascular Devices HHS/FDA/CDRH. Focus of Presentation. Potential questions related to the interaction between cell suspension and catheter

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Cardiac Catheters for Delivery of Cell Suspensions

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  1. Cardiac Catheters for Delivery of Cell Suspensions Donald Nick Jensen, DVM, MS Division of Cardiovascular Devices HHS/FDA/CDRH

  2. Focus of Presentation • Potential questions related to the interaction between cell suspension and catheter • Standard questions for consideration - suggested to all sponsors of IND’s / cell delivery cardiac catheters • Example cell delivery methods / devices • Infusion of cells into coronary artery during balloon occlusion of artery • Percutaneous, intracardiac, needle-tipped injection catheter for transendocardial injection into myocardium • No cardiac catheters for cell delivery approved in U.S. FDA/CDRH/DCD

  3. Infusion of Cells into Coronary Arteries • Advantages - simplicity, ease of use • Not suitable for all cell suspensions? • Requires migration of cells from vasculature into myocardium? • Potential for embolization / microembolization? • Demonstrated during case series • Acute MI (hours-to-days), commonly following emergency PCI / stenting • Chronic MI / ischemia FDA/CDRH/DCD

  4. Use of Balloon Catheters • Balloon catheter occludes artery proximal to treatment region • Cells infused via balloon catheter lumen or via infusion catheter lateral to balloon • Allows infusion at > arterial pressure • Increase dispersion within vasculature? • Increase adhesion of cells to endothelium? • Increase migration of cells into myocardium? FDA/CDRH/DCD

  5. Strauer BE, et al. Circulation 2002;106:1913-18.

  6. Ballon Angioplasty Catheters • Designed to “stretch” occluded arteries and/or stents to desired diameters • Can use balloon for occlusion. If guidewire lumen can potentially use for infusion of cell suspension. • Considerations if angioplasty catheters are used for infusion of cell therapies • Potential for catheter materials to adversely affect viability / functionality of cells? Also - guidewire lumens commonly coated with lubricants. FDA/CDRH/DCD

  7. Catheter – Cell Compatibility FDA/CDRH/DCD

  8. Considerations - Angioplasty Catheters • Balloon designed to stretch artery must instead occlude artery without damaging artery wall • Arterial stretch during angioplasty induces stenosis • Essential to develop / demonstrate safe methods for balloon inflation during delivery of cell therapies • Balloon pressure-diameter relationship (compliance) varies widely among angioplasty catheter designs • Methods for one catheter may not work for others • Concentrated cell suspensions may clog lumen? • Balloon catheter guidewire lumens / connectors not tested to sustain high pressures? FDA/CDRH/DCD

  9. Needle-Tipped Injection Catheters • Advantages • Direct injection into desired myocardial locations • Potentially usable with all cell types • Cardiac catheter or system (catheter plus sheaths) with retractable, distal injection needle • None approved for sale in U.S. • Some design requirements potentially similar to cardiac ablation catheters, endocardial biopsy caths • Tip must be steerable / deflectable to various locations • Sufficiently stiff to maintain tip contact with cardiac wall FDA/CDRH/DCD

  10. Perin EC, et al. Circulation 2003;107:2294-2302.

  11. Concerns - Needle Injection Catheters • Clogging of lumen by cell suspension? • Small injection volume, concentrated cell suspension • Small injection needle / lumen diameter • 20+ injections per treatment session • Is cell viability / functionality adversely affected by lumen materials or by shear force? • Inadvertent injection into LV cavity? (systemic) • May be difficult / impossible to ensure continuous contact between catheter tip and endocardium? • Kalman JM, et al. American Heart J 1997;133:8-18. FDA/CDRH/DCD

  12. Concerns - Needle Injection Catheters • Control / limit - maximum needle extension? • Avoid injection / laceration of surrounding organs • Safety if cell suspension is delivered pericardial / thoracic / systemic (via lymphatics)? • Curves in catheter may alter needle extension • Possibly difficult to avoid occasional injection into pericardial space if heart has minimal epicardial fat? • Locally “thin” regions of the LV wall • Compression / stretch of LV wall by catheter tip • Force of injection may separate myocardial and epicardial cells? FDA/CDRH/DCD

  13. Concerns - Needle Injection Catheters • Are depth and “spread” of injection critical aspects of therapy? • Does injection of cells near “more ischemic” endocardial region = injection near less ischemic epicardium? • Is a minimally dispersed bolus of cells at each injection site = wider dispersion of cells at each injection site? • Catheter design, cell suspension characteristics, injection speed - all may affect depth and spread? • Will different injection catheters deliver the same therapy? • Animal studies can characterize depth and spread • Is it important to characterize “therapy delivered” ? FDA/CDRH/DCD

  14. Additional Discussion • Nick Jensen Division of Cardiovascular Devices (301) 443-8517, x171 DNJ@cdrh.fda.gov • Elias Mallis Branch Chief, Division of Cardiovascular Devices (301) 443-8517, x177 EYM@cdrh.fda.gov FDA/CDRH/DCD

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