# Presentation: 130785

## Aortic Anastomotic Devices Adverse Event Report Analysis 

- Julia Marders, RN, MS
- Division of Postmarket Surveillance
- Office of Surveillance and Biometrics

## Outline

- FDA’s Medical Device Reporting System (MDR)
- description
- limitations
- Search methodology
- Findings
- Conclusions
- Considerations
- Questions for panel

## MDR – A Brief Description

- Nationwide passive surveillance
- Mandatory and voluntary reporting
- Types of reports

## Limitations of MDR

- Underreporting
- No incidence data
- Biased reporting
- Uncertain causality

## Methodology for Data Retrieval

- Product code
- May 24, 2001 -  March 1, 2004

## Overall Counts

- TOTAL REPORTS			213
- 2001  -	  11
- 2002  -	  53
- 2003  -	145
- 2004  -	    4
- DEATH				  23
- INJURY				185
- MALFUNCTION		           5

## Patient Characteristics

- Age	   	  35 – 83 years
- Gender
- Male	**	****   **52%
- Female	   	   24%
- Unspecified        24%
- Event Location
- Domestic	   81%
- Foreign		     7%
- Unspecified	   12%

## DEATHSN= 23

- Time of occurrence: 	within 18 days
- Problems
- Occlusion / Thrombus		12*
- Aortic Dissection			  7*
- Device Detachment		  6*
- *One report with both dissection + detachment
- * One report with both thrombus + detachment

## Death report:  Example

- 	A patient was implanted with an aortic anastomotic device during an off- pump procedure.  No difficulties were encountered with loading or deployment of the device.   Recovery was good for  40 hours when the patient suddenly lost consciousness after a dramatic drop in blood pressure.  CPR was initiated and blood appeared in the drains.  At re-operation, the aortic connector was detached from the aorta and the patient died after 10 minutes.  The autopsy revealed the cause of death was hemorrhagic shock.

## INJURIESN= 185

- Most frequently reported patient problems
**STENOSIS****	****	****	****	****82**
**OCCLUSION/THROMBUS****	****	****60**
- Time of occurrence (days): stenosis/occlusion
- Within 30 		 9
- >30 to 90		 9
- >90 to 180	          10
- >150 to 279		 2

## MALFUNCTIONSN= 5

- Anchor tip closed (1)
- Aortic plug not seen (2)
- Aortic laceration  (1)
- Connector failure (1)

## CONCLUSIONS

- Reports of SERIOUS OUTCOMES
- Reports suggest DEVICE-RELATED occurrences
- Reported events reflect SHORT-TERM experience

## Considerations

- Failure analyses of adverse events
- Risk/benefit data

## Questions for panel consideration

- Is long-term failure rate data collection necessary?
- Should studies comparing patient outcomes between those with standard suturing vs. sutureless anastomotic devices be done?
- Is further study of device-related events needed?

## Vascular Anastamotic Devices for CABG

- Dina Fleischer, Branch Chief, Circulatory Support and Prosthetics Devices Branch
- Kachi  Enyinna, Scientific Reviewer, Circulatory Support and Prosthetics Devices Branch
- Wolf Sapirstein, MD, Medical Officer

## A Clinical Imperative

**Scope of Problem**
- 350,000-500000 procedures per year
- 2.5 CABG per patient

## Modification to CABGProcedure

- Venous Conduits
- CASS
- Induced Ventricular Fibrillation
- Hypothermic anoxic arrest
- Cardioplegic arrest
- Arterial Conduits
- Minimal Access Direct CABG (MIDCAB)
- Beating Heart CABG (BH and OPCAB)

## CABG Morbidity	

- Median Sternotomy
- Incisional Trauma -> MIDCAB
- Cardiopulmonary Bypass
- Inflammatory/ImmunologicBHCAB   OPCAB
- Neuro-cognitive Complications.
- Extracorporeal Circulation (OPCAB)
- Aortic Manipulation  (ITA; T-grafts)
- Anastamotic Devices as Morbidity Prophylactic

## CABG  Patency

- Autogenous Venous Grafts
- 5% failure peri-operative
- 10-15% at 1 year
- 1-4% per year  50% at 10years
- Internal Thoracic Grafts
- 95-98% peri-operative patency
- 90-95% 1 year patency

## CABG FailureAttribution of Cause

- Peri-operative:
- Technical construction
- Inadequate run-off
- Inadequate conduit
- 6 month - one year
- Neo-intima hyperplasia
- Native CAD progression
- Continuum from 6 months
- CAD (Native and Conduit vessel)

## Anastamotic DevicesBenefits

- Standardized anastamosis
- Rapidity of construction
- Avoidance of aortic clamping
- Diminished manipulative trauma to vessels
- ?Conduit protection from injury
- Facilitates OPCAB, MIDCAB, BHCAB

## Anastamotic DevicesDisadvantages

- Compliance mismatch
- Material promotes local thrombus and inflammation.
- Conduit and/or vessel trauma by device deployment
- Flawed design of anastamosis prejudicial to laminar flow
- Revision unfriendly

## Assessment Problems  

- CABG failure multifactorial
- Instruments
- Invasive
- Non-invasive (Stress Echo/EKG:MRI:
-                              Spiral CT:EBT)
- Observational vs Experimental Study
- Control: Randomized vs Concurrent RCT
- Duration of Study

## Variables Confounding Study Design 

- Multi-factorial causes CABG failure
- Proximal vs Distal Anastamosis Devices
- Vein vs Arterial Conduit
- Differences in Anastamosis devices’ Design

## Study Template	

- Randomized
- BHCAB vs CABG
- Stratified:
- Vein conduit
- Arterial Conduit
- Aortic vs Distal
- Similarity vs Superiority Trial:
- LCL 5%
- 95% patency LIMA @ 9 months
- 90% patency Vein  @ 9 months
- Sample Size

## QUESTIONS FOR PANEL

**Vascular Anastomosis**
**Devices for CABG **
**Panel Meeting**
**March 18, 2004 **

## Trial Design

- Please comment on the choice of control in the clinical trial required to evaluate vascular anastomosis devices for CABG.  The gold standard of sutured CABG anastamoses has a well documented history of over thirty years:

## Trial Design

- Can historical data from sutured CABG anastomosis device trials be used as the control in the device studies?

## Trial Design

- Alternatively, are concurrently performed CABG controls necessary given the multi-factorial causes of CABG failure, e.g. technical construction, extent and progression of native vessel disease, condition of conduit and progression of intima hyperplastic and atheromatous degeneration, and the introduction of drugs for mitigation of arteriosclerotic disease (CAD)?

## Trial Design

- If these trial designs are inadequate, should randomized controlled clinical trials be performed?

## Trial Design

- With regard to device placement and device design, please address the following:
- Given the considerable differences between the proximal and distal CABG anastomoses, what, if any, differences in study criteria should be required?

## Trial Design

- Are there certain aspects of the clinical study design (e.g. length of follow-up, endpoints) that should be required for all devices irrespective of device form and function?  For example, the U-clip performance closely duplicates that of a suture, whereas the Symmetry has greater similarity to a stent.
- It is rarely possible to determine the cause of conduit failure.  Can you suggest criteria to determine whether a failure is device related?

## Trial Design

- Do you believe that the significant differences between an arterial conduit and a venous conduit warrant distinct study criteria and assessment for each?  If so, please identify these criteria and analyses.

## Trial Design

- Should the primary effectiveness endpoint be graft patency alone, or include both graft patency and myocardial perfusion?

## Endpoint Evaluation

- With regard to appropriate patient follow-up:
- In view of the possible persisting risk of failure of some mechanical anastomosis sites, distinct from progression of native vessel disease, what duration of follow-up is advisable for pre-market evaluation?

## Endpoint Evaluation

- Should post-market follow-up be required to assess long term device effectiveness?  If so, please define the appropriate length of follow-up after primary patency evaluation.

## Endpoint Evaluation

- Can non-invasive measuring instruments, e.g., echocardiography, ultrafast spiral CT, MRA, EBT, etc., be used for primary assessment of graft patency or is angiographic follow-up necessary?  And at what time points should patency be assessed?