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Recapitulation of the Opening Plenary Session: San Diego 2017

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Vincent Valentine, MD
University of Alabama Birmingham
Birmingham, AL, USA

The Opening Plenary Session of the 37th Annual Meeting and Scientific Session in San Diego began with Jeff Teuteberg's Program Chair's Report. The number of abstracts submitted in 2006 to 2017 has doubled from just under 800 to 1,633, with nearly 85% accepted this year. The ISHLT continues to have global representation with members from 38 different countries, growth from Asia and South America, and a truly international balance of the Program Committee. The major theme in Teuteberg's report was the clustering of ideas, which generated thematic talks and poster presentations.

Josef Stehlik followed with the Registry Report - the main theme was 200,000. A donation, an award or the number of patients who have undergone cardiothoracic replacement. From the Thoracic Transplant Registry, the focus was allograft ischemic time. In Pediatric Lung Transplantation, although there has been an incremental rise in allograft ischemic time to 6+ hours approaching 50% of transplants, no correlation of treated rejection or BOS with ischemic time was observed. However, there was a difference in survival with a separation beginning in the first three postoperative months. At five years, pediatric lung recipients with ischemic times between 4-6 hours had a 25% better survival than the 6+ hours cohort. In adult lung transplantation, the ischemic time is 0-<6 hours in 90% of single lung recipients, whereas the ischemic time is >6 hours in 40% of bilateral lung recipients. There is an incremental increase in treated rejection events at 1 year in just over 30% patients with ischemic times >6 hours vs 25% and 20% in those with ischemic times 4-<6 hours and 2-<4 hours, respectively. With respect to BOS, there were no clinically relevant differences other than a hint that the >6 hour group had a better BOS-Free Survival, yet no difference in overall survival.

In pediatric heart transplantation, no difference in treated rejection or chronic allograft vasculopathy with respect to ischemic time was observed; however, there was a difference in survival with separation beginning in the first three postoperative months. The hazard ratio for death at one year was at unity and up to 1.5 in the 6+ hour cohort. In adult heart transplantation, although there were more than 20% patients treated in the first year in the 6+ hour cohort vs just over 10% in the 0->2 hour group, p<0.05, there was no difference in ischemic time and allograft vasculopathy across all groups. However, there was a difference in survival with a separation beginning in the first three postoperative months across all groups with respect to ischemic time. Also, younger donors had a lower hazard ratio of death in the first year with respect to ischemic times.

Dirk Van Raemdonck presented the report on Donation after Circulatory Death Lung Registry. The 30-day survival in patients with donors after circulatory death (DCD) vs donors after brain death (DBD) were similar; however, three-year survival in the DCD group was 10% better, p<0.001. Anne Dipchand presented the data from the Pediatric Heart Failure Registry. From 16 active centers, 81 patients have been enrolled.

Jim Kirklin presented the 2017 IMACS Registry Report. There are 35 countries represented with 14,062 patients enrolled. According to device strategy, 43% for destination therapy, 29% candidacy to transplant and 28% listed for transplant. The 1 and 2-yr survival for continuous flow LVAD/BiVAD implants is 80% and 70%, respectively. Primary causes of death include: multisystem organ failure (20.5%), right heart failure (20.4%), neurological event (19.1%), withdrawal of support (9.9%) and infection (8.0%). Early and constant hazard risk factors were older age and female gender. Other early hazards included: high BMIs, ventilator or dialysis need within 48 hours of implant, concomitant surgery, and BiVAD. Survival according to age group show >75% survival at four years in those <30 years and 30-49 years. Whereas, 4-yr survival in the 50-69 yr and ≥70 yr was roughly 60% and 40%, respectively. The major adverse events were: infection (38%), bleeding (36%), neurological dysfunction (13%), respiratory failure (11%), device malfunction (2%) and arterial non-CNS thromboembolism (1%). The 2017 goals are to increase recruitment of hospitals and collectives, expand IMACS research and increase research proposal submissions.

Following the Registry Reports, Maryl Johnson delivered her journey to and through the ISHLT Presidency. She began her report with a letter from Dr. John Schroeder from Stanford and a quote from Gloria Steinem, "The art of life isn't in controlling what happens, which is impossible; it's in using what happens," both of which inspired her to pursue a career in heart transplantation. She reviewed and highlighted the progress of the 2016 to 2020 Strategic Framework.

She shared a couple other quotes from an unknown author, "Volunteers are not paid - not because they are worthless, but because they are priceless," and "If you want to go fast, go alone; if you want to go far, go together." She finished her address with "One doesn't discover new lands without consenting to lose sight of the shore for a very long time." - Andre Gide.

The featured abstract presentation followed beginning with Dr. Carmelo Milano from Duke, who presented the results of the ENDURANCE Supplement Trial. Although the difference in neurological injury at 12 months between the HVAD and control groups were small (2.6%) without meeting the primary endpoint, HVAD was statistically superior with respect to freedom from death, disabling stroke, device exchange or urgent transplant at 12 months. Dr. Daniel Goldstein from Montefiore then presented the results of the Heartmate 3 (Momentum 3) Pivotal Trial. This trial showed improvement in clinical outcomes with the HM3 compared to HMII. Younger age and HM3 vs HMII were independently associated with a greater likelihood of primary endpoint success. However, sex, therapeutic intent (BTT or DT), severity of illness, and race, when adjusted for age, did not influence primary endpoint success.

Dr. Stuart Jamieson closed the 37th Annual Opening Plenary Session as this year's Pioneer Award Recipient with his lecture entitled "Standing on the Shoulders of Giants." He shared and summarized his personal odyssey, which began on a ranch in Rhodesia (now Zimbabwe) where he grew up with a zebra, an ostrich and a giraffe. In 1947, there was no heart surgery, "if you touched the heart it would stop" - to reach the inside of the heart was impossible. There were many giants. First, F. John Lewis - with hypothermia, on September 2, 1952, made a bold and innovative move to fix an atrial septal defect in need of repair for the five-year old, Jacqueline Johnson. Second, C. Walton Lillehei - with cross circulation was able to perform 45 operations on patients with complex congenital heart conditions in a year of which 32 survived (70%).

Stuart went to Medical School at the University of London affiliated with St Mary's Hospital where penicillin was discovered, had strong immunology, andwhere early kidney transplants took place. He described two more giants - Barnard and Shumway, both of whom studied under Lillehei. By 1968, 101 heart transplants were performed by 64 teams from 22 countries. Then the tragic record of heart transplants was plastered on the cover of Life magazine in September, 1971 - a new report on an era of medical failure. He then shared his publications on the Xenograft hyperacute rejection. A new model from Transplantation, 1974 and Hyperacute rejection of guinea pig to rat cardiac xenografts in the Journal of Pathology, 1975. In response, Norman Shumway quips and quotes, "Xenograft Transplantation is in the future and always will be..." The giant, Shumway continued his pursuit of laboratory work supporting the clinical operation of heart transplantation. Mention of Matt Paneth from the Brompton Hospital, who also studied under Lillehei showed interest in Heart Transplantation. The next giant Jean-Francois Borel - the wonder drug - cyclosporine (the vial of golden liquid) was the first to report on the immunosppressive qualities of this fungal derivative in 1976. From Shumway's lab, Jamieson reported on the "Survival of Cardiac Allografts in Rats treated with Cyclosporin A," Surgical Forum, 1979. This was followed by "Cardiac Allograft Survival in Primates treated with Cyclosporin A," Lancet 1979, Jamieson et al again out of Shumway's Lab. Then the first human heart transplant to use cyclosporine, July 4, 1979 at age 20, today still with us at age 58.

The Society emerged with Stanford, University of Virginia and Tucson as the only active programs in heart transplantation. By 1980, 314 heart transplants were performed, 2/3 from Stanford, of 199 cases, 75 remain alive today. By the time of the second meeting of the Society, MGH supported by the NEJM decided against heart transplantation; therefore, no funding by Medicare. The first Official meeting of the Society occurred in San Franscisco, March 1981, the International Society of Heart Transplantation. Animal experiments in the laboratory from Stanford led to the first human heart transplant using cyclosporin. Cyclosporine became available for general use in 1983, then Heart Transplantation became widely practiced.

By 1980, only 38 attempts at lung transplantation were done and only one left the hospital, died within a few months. Clinical efforts in Heart-Lung Transplantation were performed by Cooley, Lillehei and Barnard. It was back to the Stanford Laboratory. On March 9, 1981 with Bruce Reitz, John Wallwork, Stuart Jamieson and Norm Shumway performing the first successful heart-lung transplantation on Mary Gohlke, who had been previously diagnosed with primary pulmonary hypertension.

Then in 1986 to the Midwest, Stuart went to work among his revered giants, Lillehei and Lewis. He brought the first heart-lung and double lung transplant to the Midwest. Stuart moved on to San Diego and brought the first heart-lung, lung, double lung and living-related transplant there, along with the first lung transplantation program to be Medicare certified. In an effort to increase donor supply, focus was made to minimize heart-lung transplant, use intra-cardiac repair when possible and perform pulmonary endarterectomy for thromboembolic pulmonary hypertension.

Stuart Jamieson shifted gears of his Pioneer Award Lecture towards pulmonary endarterectomy. From Lungdahl 1928 with the first description of chronic pulmonary embolism, to the nearly 200 cases described by Hollister and Cull in 1956, the first operation by Blalock in 1948 and the first successful operation by Hufnagel in 1962. Stuart went on to outline the UCSD experience over 40 years with modification of the operation. Instruments were developed, classification proposed and the operation was taught worldwide with Jamieson's seminal works in the Annals of Thoracic Surgery in 2003 on "Pulmonary endarterectomy: experience and lessons learned in 1500 cases."

Stuart concluded this standing room with a standing ovation, "if we see further it is because we sit upon the shoulders of giants."

Disclosure Statement: The author has no conflicts of interest to disclose.

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