PREVENT trial protocol lowers incidence of LVAD thrombosis
Left ventricular assist devices (LVADs) provide lifesaving therapy to many patients with end-stage heart failure, whether they are used as a bridge to transplant or as destination therapy. Technical improvements in device and battery design have made this therapy feasible for many patients.
Currently, almost half the patients waiting for transplant at Mayo Clinic's campus in Rochester, Minnesota, are supported by an LVAD. Individuals receiving an LVAD as destination therapy tend to be older, have significant comorbidities, and are not transplant candidates, but many regain an excellent quality of life after LVAD implantation.
Device thrombosis has always been a vexing problem, because not all LVAD components are biocompatible. Patients who received early pulsatile-flow VADs were at a significant risk of embolic stroke from thrombus formation in these larger, bulky devices. Current-generation continuous-flow devices have a more compact design, predisposing them to thrombosis of the entire pump.
The risk of thrombosis is highest early after device implantation; prior studies have demonstrated early pump thrombosis rates of up to 8.4 percent in patients receiving the HeartMate II (Thoratec/St. Jude Medical) LVAD. Most device management protocols are institution specific and highly variable, especially regarding anticoagulation, making comparison difficult. The nonrandomized Prevention of HeartMate II Pump Thrombosis Through Clinical Management (PREVENT) trial evaluated the effect of treatment with a standardized management protocol on the incidence of pump thrombosis during the first three months after device implant.
- Create an inferiorly deep and laterally positioned pump pocket.
- Make sure the inflow cannula is positioned parallel to the septum.
- Avoid right ventricular compression by carefully positioning the outflow graft.
- Place the pump below the diaphragm and anchor it.
- Start titrated heparin within 48 hours post-implantation.
- Initiate warfarin within 48 hours and target an INR of 2.0 to 2.5.
- Two to five days post-implantation, start aspirin therapy at 81 to 325 mg a day.
- Make sure the pump runs at a speed greater than 8,600 rpm and preferably greater than 9,000 rpm.
- Mean arterial pressure should be maintained at less than 90 mm Hg.
Methodology and results
This observational study involved 300 patients (83 percent male, mean age 57 years, 78 percent destination, 22 percent bridge to transplant) with no prior mechanical circulatory support at 24 transplant centers.
Suspected pump thrombosis was defined as having two of the following:
- Abnormal pump parameters
- Worsening heart failure
It also needed to be accompanied by intravenous anticoagulation treatment, pump explantation, urgent transplantation, stroke or death.
By the three-month follow-up, there were 12 suspected thrombotic events in 11 patients.
Confirmed pump thrombosis had the same criteria but also included documented, photographic evidence of a thrombosis. Of the 12 suspected events, nine were confirmed (2.9 percent, less than half of historical rates). The outcomes for these confirmed events were seven pump exchanges and two urgent transplantations.
In the patients who had nonconfirmed pump-thrombosis events, one had a pump exchange and one died, but neither was found to have thrombus. The third patient remains under supervision.
The overall survival rate was 91 percent at 90 days post-implantation, and survival free of pump thrombosis was 88 percent. For adverse events, there was an 18 percent rate of GI bleeding at three months, a 16 percent rate of right heart failure, a 3 percent rate of ischemic stroke and a 2 percent rate of drive-line infection.
When the adherence to the overall recommendations and its impact on outcomes were examined, the results showed no significant difference in confirmed pump thrombosis, but there was a trend toward more-adverse cases for those with partial adherence versus those with good adherence (4 percent versus 1.9 percent, respectively).
In addition, combined endpoint of suspected thrombosis, hemolysis or ischemic stroke was significantly greater with partial adherence (12.1 percent versus 5.1 percent, P < 0.05).
A study presented earlier at the International Society for Heart and Lung Transplantation (ISHLT) meeting showed that the new HeartMate 3 had 80 percent survival in 50 patients in Europe implanted with the LVAD and no incidence of pump thrombosis; however, this device is not yet approved for use in the U.S., and worldwide experience is extremely limited.
"The HeartMate II LVAD will continue to be implanted in the U.S. for the foreseeable future," says Simon Maltais, M.D., Ph.D., a cardiovascular surgeon at Mayo Clinic in Rochester, Minnesota, and lead investigator of the study, during his presentation of trial results at the ISHLT 2016 Annual Meeting and Scientific Sessions. "Based on these results, we recommend adoption of the PREVENT recommendations for all patients with a HeartMate II LVAD to reduce pump thrombosis risk."