On October 26, 2016, the FDA provided an update and additional information regarding SynCardia Systems, Inc.'s Temporary Total Artificial Heart (TAH-t) Companion 2 Driver System (C2 Driver System), as well as information of recent events with an additional SynCardia pneumatic driver system, the Freedom Driver System. The TAH-t functions as a bridge to a heart transplant in a small population of heart failure patients with severe bi-ventricular failure. There has continued to be a higher mortality rate for the subgroup of patients requiring pre-implant circulatory rescue interventions when using the C2 Driver System compared to those using the CSS Console.
The mortality rates for patients who did not require pre-implant circulatory rescue interventions were similar for the C2 Driver System compared to the CSS Console. The most recent post-approval study results suggest that there is also a difference in clinical performance between the C2 Driver System and the CSS Console in terms of neurological adverse events.
As a condition of approval of the C2 Driver System, the FDA required SynCardia to conduct a post-approval study assessing post-market performance. The study relies on data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), and compares outcomes for patients who were initially supported with the C2 Driver System and the CSS Console during the same time period (implanted on June 20, 2012, or after).
On June 15, 2015, the FDA posted a letter informing the health care community that preliminary post-approval study information suggested a higher mortality rate for a subgroup of patients requiring pre-implant circulatory rescue interventions when using SynCardia's TAH-t C2 Driver System as compared to the previous generation driver, the Circulatory Support System (CSS) Console. Since then, additional interim post-approval study results have indicated a higher risk of neurological adverse events for patients supported by the C2 Driver System compared to patients supported by the CSS Console. The mortality rates for patients who did not require pre-implant circulatory rescue interventions were similar for the C2 Driver System compared to the CSS Console.
The cumulative number and percentage of patients who required pre-implant circulatory rescue intervention and died within three months of TAH-t implant are stratified by the patients' initial support driver. Specifically, among the 80 patients with pre-implant circulatory rescue interventions, mortality was 39 percent in second generation C2 Driver System users, compared to 25 percent in first generation CSS Console users. For the 107 patients who did not require pre-implant rescue intervention, the mortality rate up to three months post-implant was 27 percent in C2 Driver System users, compared to 21 percent in CSS Console users. It should be noted that statistical testing for mortality results is not appropriate at this time, given that the post-approval study is ongoing and the primary endpoint is survival rate.
The most recent post-approval study results suggest that there is also a difference in clinical performance between the C2 Driver System and the CSS Console in terms of neurological adverse events.
The INTERMACS Neurological Adverse Event (AE) outcome is a composite of several separate adverse events including: transient ischemic attacks, confusion, ischemic/embolic stroke, hemorrhagic stroke, strokes from other causes, seizures, encephalopathy, and other events. The INTERMACS Neurological AE rates from the first three months after TAH-t implant were provided for patients initially supported by the C2 Driver System and for patients initially supported by the CSS Console. The Neurological AE rate in the first three months post-implant is higher for patients initially supported with the C2 Driver System (31 percent) compared to patients initially supported with the CSS Console (16 percent).
These results are not adjusted for potential confounders, and they were not further stratified by pre-implant circulatory rescue intervention status. The Neurological AE rate will continue to be monitored, and additional analyses will be performed as appropriate in the future.
Post-approval studies of the TAH-t and investigation into these issues are ongoing. Researchers do not know the root cause for these observed differences, and the existing data is limited. INTERMACS only captures information regarding the initial driver used to support TAH-t patients, and at this time, only unadjusted interim rates are available. Although there is concern about the difference in outcomes between the C2 Driver System and the CSS Console, it is recognized that the C2 Driver System may be the best option for circulatory support for some patients.
In addition to the C2 Driver System and the CSS Console, a third pneumatic driver system, the SynCardia Freedom Driver System, is also available to power the SynCardia TAH-t. The Freedom Driver System is portable and can be used outside of the hospital, allowing some TAH-t patients to return home while on the device.
The FDA is aware of recent reports of serious, life-threatening TAH-t device malfunctions involving the Freedom Driver System. These reported malfunctions have included sudden cessation of TAH-t pumping without warning alarms or recognizable signs of impending malfunction (such as a change in sound during the Freedom Driver System's operation). The Freedom Driver System was also the subject of a Class 1 Recall initiated on August 7, 2015, but these recent reports appear to be unrelated to the issues that prompted the recall last year.
The FDA is working with SynCardia and clinicians to fully assess reports of malfunction involving the Freedom Driver System. In light of these recent reports, the FDA advises that clinicians review the Operator Manual's specific precautions regarding Freedom Driver System use outside of a hospital environment, and carefully consider individual patient circumstances when evaluating the Freedom Driver System as a treatment option.
For the other drivers the FDA recommendations are similar. Carefully consider these mortality and neurological adverse event results, and device malfunction reports when making treatment decisions and device selection, and discuss the risks and benefits of these devices with patients.
See the Safety Announcement
See the FDA Medical Devices Alert
See also Medical Law Perspectives, September 2016 Report: Stroke: Challenges, Risks, and Liability Issues
See also Medical Law Perspectives, February 2015 Report: Mending a Broken Heart: Malpractice Risks in Diagnosing and Treating Heart Disease
See also Medical Law Perspectives, December 2013 Report: Thicker Than Water: Liability When Blood Clots Cause Injury or Death
See also Medical Law Perspectives, November 2013 Report: Diagnosis and Treatment of Heart Attacks: Liability Issues