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I Think We Need A Bigger Boat

by Scott Feitell and Anders Andreasson

Saturday's Plenary Session featured some keynote presenters focusing on the dire shortage of organs that, unfortunately, remains an ongoing theme of these ISHLT meetings. Well, this morning, Dr. Lynne Stevenson presented further data to distress even the most hungover of us in the audience (come on, that Thoratec group put on a good party last night, we all know that). While the Department of Health and Human Services is still tabulating how many cocktail shrimp you ate courtesy of big pharma to place on their Sunshine website today, Dr. Lynne Stevenson jumped right into the biggest problem we face today. Too many sick patients, and not enough hearts.

She took a unique perspective, starting off with an analogy of the sinking ship with a small lifeboat that can only hold so many patients to drive home the point that the sharks are circling our patients if we don't figure out a better way to allocate the limited resources we have. One point she continued to drive home is that the way we list our patients on UNOS for transplant is inefficient and makes the list look artificially large. She points out that almost no Status 2 patients get transplanted anymore (particularly on the east coast) and that not all 1A patients are created equal. She drove this home by quoting her father, Stanley L. Warner, who said, "Anyone who has reached the age of 21 and thinks that life is fair has a learning disability."

She also keenly pointed out that reducing just 20% of those patients listed every year would provide a more reasonable wait list and would provide better access to those who needed hearts. Clearly there are no easy ways to do this, but reevaluating borderline patients with too many risk factors and ensuring patients with higher chances of good outcomes could be a start. She also points out the psychological toll the list takes on patients, especially those who are so-called "bridge to decision" and are kept in limbo with an LVAD with no clear end in site, whether it be destination therapy, or in fact a transplant.

In an effort perhaps to expand the donor pool, Dr. Abbas Ardehali offered data on the PROCEED II trial. Using an Organ Care System (OCS), which can keep a harvested heart "alive and beating" before implantation, his group hopes not only to expand the donor pool, but eliminate such concerns such as cold ischemic times from the equation that are always an issue with the old fashioned "ice chest" method of transporting organs." This novel device provides blood flow, oxygenation nutrients, and inotropes to the explanted donor heart while it is in transit. It also monitors continuously hemodynamic parameters and biochemical markers of ischemia and damage. It could potentially exponentially expand heart transplants in a multitude of ways.

The study was set up as a non-inferiority and safety trial, and luckily it seemed to meet all its primary and secondary endpoints. Most interestingly, I found, is that five potential donor hearts in the study that were in the OCS were found to have abnormally high lactate levels during monitoring which led to pathologic review. All five hearts had significant pathology that would have limited graft survival had they been used. It is not hard to see the usefulness of this device in future evaluation and harvesting of organs. Perhaps this device can one day be used to evaluate resuscitated hearts before implanting into a new host as Dr. Ardehali pointed out.

Cardiac transplants since Barnard have flashed on the cover of Time Magazine (and presumably much earlier than that) have been regarded as something close to science fiction. However, since Professor Shaf Keshavjee gave his iconic talk at TED a few years back, the lung has had its much desired revenge as the audience awed at the possibility of perfusing and ventilating a pair of lungs outside of the human body.

In the Invited Lecture: Frontiers of DCD in Thoracic Transplantation, Prof. Thomas Egan gave an attention-grabbing talk with the key point being that lung recovery from uncontrolled DCDs reassessed on EVLP for transplantation is "an innovative disruptive technology poised to revolutionize therapy for end-stage lung disease". With the potential of increasing the availability of lung transplant donors only in the U.S. with 40,000 lungs a year, Prof. Egan is convinced that the pioneering work of Dr. Moradiellos and colleagues in Madrid must be followed up and adopted into a wider clinical practice to make lung transplantation a reality for more waiting list patients with life threatening lung disease.

As organ perfusion has become one of the "hot topics" in all fields of transplantation, ex-vivo lung perfusion (EVLP) continues to lead its progression and is featured in over 40 presentations at this year's Annual Meeting. The available EVLP methods are being investigated in four ongoing multicenter trials (NOVEL, DEVELOP-UK, EXPAND, and INSPIRE), and the full safety, cost effectiveness and potential impact on graft availability would shortly be revealed. In the wellvisited Plenary Session on Saturday, the one-year outcome of the NOVEL lung trial was presented as a featured abstract by the now established front figure Dr. Pablo Sanchez.

The NOVEL trial was the first prospective multicenter trial designed to evaluate the safety of EVLP as a method to screen and identify good quality grafts from the donor pool of lungs rejected for transplantation. It is a non-randomized open label study, where 84 lung transplant recipients were enrolled with the start in August 2011. 42 EVLP transplants with lungs initially found unusable for transplant and rejected by multiple centers (median of 39 times according to Dr. Sanchez) and 42 standard controls. The early outcomes have been very promising, and the primary endpoint of 30-day survival was not significantly different between patients that received EVLP or standard criteria lungs (98% vs. 100%, p=1).

Dr. Sanchez said, "We are excited with the results and believe that the NOVEL trial has helped in establishing the rationale to extend the donor pool and permit the acceptance of donor organs that might have otherwise been not transplanted."

This has, for obvious reasons, also been received with great excitement in the camp of the study sponsor XVIVO Perfusion AB, which has recently had the trial EVLP machine, XPSTM, CE marked for EU distribution and has progressed in the FDA approval process.

Many congratulations to the trial investigators for managing to complete this important multicenter trial. "He who waits gets a tailwind, and he who rows, a harbor" ... right?!

Disclosure Statement: the authors have no conflicts of interest to report.

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