cardiac catheters for delivery of cell suspensions donald nick jensen, dvm, ms division of...
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Cardiac Catheters for Delivery of Cell Suspensions
Donald Nick Jensen, DVM, MS
Division of Cardiovascular Devices
HHS/FDA/CDRH
FDA/CDRH/DCD
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
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
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?
• Strauer BE, et al. Circulation 2002;106:1913-18.
FDA/CDRH/DCD
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
1. Potential for catheter materials to adversely affect viability / functionality of cells? Also - guidewire lumens commonly coated with lubricants.
FDA/CDRH/DCD
Catheter – Cell Compatibility
FDA/CDRH/DCD
Considerations - Angioplasty Catheters
2. 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
3. Concentrated cell suspensions may clog lumen?
4. Balloon catheter guidewire lumens / connectors not tested to sustain high pressures?
FDA/CDRH/DCD
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
• Perin EC, et al. Circulation 2003;107:2294-2302.
FDA/CDRH/DCD
Concerns - Needle Injection Catheters
1. Clogging of lumen by cell suspension?• Small injection volume, concentrated cell suspension
• Small injection needle / lumen diameter
• 20+ injections per treatment session
2. Is cell viability / functionality adversely affected by lumen materials or by shear force?
3. 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
Concerns - Needle Injection Catheters
4. 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
Concerns - Needle Injection Catheters
5. 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
Additional Discussion
• Nick Jensen
Division of Cardiovascular Devices
(301) 443-8517, x171
• Elias Mallis
Branch Chief, Division of Cardiovascular Devices
(301) 443-8517, x177