Physicians from three top institutions report an abrupt and highly troubling increase over the last two years in the incidence of pump thrombosis in patients who have received the HeartMate II left ventricular assist device (LVAD) manufactured by Thoratec.

The current investigation, was initially prompted by an observed increase in pump thrombosis at the Cleveland Clinic. This first led to an analysis performed by INTERMACS (the Interagency Registry for Mechanically Assisted Circulatory Support) which found an increase from 2% before May 2011 to 5% afterwards. But, write the New England Journal of Medicine authors, there is reason to believe the INTERMACS analysis may have underestimated the rate of pump thrombosis. (The INTERMACS data, along with other papers about the problem, have been published in a special issue of the Journal of Heart and Lung Transplantation.)

The new paper is based on pooled data from 895 patient who received the HeartMate II LVAD at the Cleveland Clinic, Barnes-Jewish Hospital, and the Duke University Medical Center . The authors report that after March 2011 the incidence of confirmed pump thrombosis within three months of implantation increased from 2.2% to 8.4% by January 2013. The same pattern was observed at all 3 hospitals and for multiple surgeons. (In a postscript added during the editing process the authors state that similar findings were found in an analysis of additional data from the University of Pennsylvania.)

Before March 2011 the median time to pump thrombosis after implantation was 18.6 months and was the result of a constant risk of pump thrombosis of 0.4% per month. After March 2011 the time to pump thrombosis decreased dramatically to 2.7 months as a result an early hazard that peaked at 2 months and then fell to a constant 0.6% monthly rate.

Overall there were 72 cases of pump thrombosis in 66 patients. 11 patients underwent heart transplantation and 19 patients had a pump replacement. Mortality was higher in the patients with a confirmed pump thrombosis.

The authors were unable to identify any predisposing factors or causes for the increase in pump thrombosis. Thoratec said the company had “performed extensive analysis on HeartMate II and have not identified any change would cause the increase observed in the INTERMACS registry.”

A rise in lactate dehydrogenase (LDH) levels was closely correlated with the increase in pump thrombosis. “We found that a sharp rise in LDH levels occurring within the first weeks after implantation often preceded and heralded confirmed pump thrombosis,” they wrote. An increase in LDH is thought to indicate hemolysis caused by thrombus formation.

The authors acknowledged that LVADs still “provide life-sustaining treatment for many patients with advanced heart failure” but said that “recommendations for LVAD therapy should account for this updated risk-benefit profile.”

Every year nearly 4,000 LVADs are implanted in the US. Approximately three-quarters of these are the HeartMate II, according to Wells Fargo analyst Larry Biegelsen. Before getting a transplant, former Vice President Dick Cheney was perhaps the most famous recipient of the HeartMate II.