EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS

SNOWMASS, COLO. (FRONTLINE MEDICAL NEWS) – Multifaceted progress in mechanical circulatory support as long-term therapy in end-stage heart failure is happening at a brisk pace, Y. Joseph C. Woo, MD, reported at the Annual Cardiovascular Conference at Snowmass.

“I believe mechanical circulatory support will ultimately surpass heart transplantation,” declared Dr. Woo, professor and chair of the department of cardiothoracic surgery at Stanford (Calif.) University.

That’s quite a prediction, especially considering the source: Stanford is where the late Dr. Norman Shumway – widely considered “the father of heart transplantation” – performed the first adult heart transplant in the United States in 1968.

In comparing the pros and cons of heart transplantation versus mechanical circulatory support, it’s obvious that device therapy is the winning strategy, Dr. Woo said. The only two areas where heart transplantation now has an edge are that it doesn’t entail lifelong anticoagulation or need for a driveline passing through the skin. But change is coming. Wireless energy transfer technology for left ventricular assist devices (LVADs) is in an advanced stage of development, and ongoing research into blood/device interactions is likely to yield solutions that obviate the need for long-term anticoagulation in patients on mechanical circulatory support (MCS), he predicted.

Dr. Woo was coauthor of an American Heart Association policy statement on the future of cardiovascular disease in the United States, which forecast a 25% increase in heart failure between 2010 and 2030 ( Circulation. 2011 Mar 1;123[8]:933-44 ). There is simply no way that heart transplantation can begin to meet the projected growing need for effective therapy in patients with end-stage disease.

Indeed, as a result of the perpetual donor shortage, only about 4,500 heart transplants are done annually worldwide. In North America the annual number has been essentially flat since 1990. Dr. Woo and his coworkers have managed to put a small dent in the donor organ shortage by developing novel techniques for surgical repair of donor hearts previously rejected by multiple transplant centers due to isolated aortic or mitral valve disease. The ex vivo valve repairs are done rapidly while the donor heart is sitting in an ice bucket prior to transplantation. But these and other efforts to enhance donor heart utilization can’t meet the growing demand.

Here’s what Dr. Woo sees as the future of MCS:

Minimally invasive implantation

At Stanford, LVAD implantations are now routinely done off-pump on a beating heart.

“We clamp only when there is a sound reason, like the presence of left ventricular thrombus, where you run the risk of embolization without the cross clamp,” the surgeon said.

Concomitant valvular surgery

At Stanford and other centers of excellence, surgeons perform additional procedures as warranted while they implant an LVAD, including atrial fibrillation ablation, revascularization of the right heart coronaries, patent foramen ovale closure, and repair of the tricuspid, pulmonic, or aortic valves.

Enhanced right ventricular management

Survival is greatly impaired if a patient with an LVAD later requires the addition of a right ventricular assist device. This realization has led to the development of multiple preoperative risk scoring systems by the Stanford group ( Ann Thorac Surg. 2013 Sep;96[3]:857-63 ) and others, including investigators at the Deutsche Herzzentrum Berlin, the world’s busiest heart transplant center. The purpose is to identify upfront those patients who are likely to later develop right heart failure so they can receive biventricular MCS from the start.

Adjunctive biologic therapies

Intramyocardial injection of 25 million allogeneic mesenchymal precursor cells during LVAD implantation appeared to be safe and showed a promising efficacy signal in a 30-patient, multicenter, double-blind, placebo-controlled, National Institutes of Health–sponsored proof of concept study in which Dr. Woo was a coinvestigator ( Circulation. 2014 Jun 3;129[22]:2287-96 ).

The goal of this research effort is to provide a cell therapy assist to the LVAD as a bridge to recovery of left ventricular function such that the device might eventually no longer be needed, he explained.

These cells are immune privileged. They can be transplanted into recipients without need for immunosuppressive therapy or HLA matching, basically as an off the shelf product. Rather than transforming into cardiomyocytes, it appears that the mechanism by which the donor cells enhance cardiac performance in heart failure is via secretion of a shower of growth and angiogenic factors.

Based upon the encouraging results of the initial study, a 90-patient, phase II, double-blind clinical trial is underway. In order to better evaluate efficacy, this time the patients will receive 150 million mesenchymal precursor cells rather than 25 million.

New technologies

The developmental pipeline is chock full of MCS devices. The trend is to go smaller and simpler. HeartWare is developing a miniaturized version of its approved continuous flow centrifugal force LVAD. The ReliantHeart aVAD, an intraventricular device less than 2.5 cm in diameter, is approved in Europe and under study in the U.S. The Thoratec HeartMate III is a smaller version of the HeartMate II, which is FDA-approved as destination therapy. And the Circulite Synergy micropump, designed to provide partial circulatory support to patients who don’t require a full-force LVAD, is the size of a AA battery.

Dr. Woo reported having no financial conflicts.

bjancin@frontlinemedcom.com

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