# Presentation: 270800

## 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
- 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.

## 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

## 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.

## 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.

## Catheter – Cell Compatibility

## 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?

## 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.

## 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.

## 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?

## 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” ?

## 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