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IN THE SPOTLIGHT: A Summary of the Plenary Sessions at ISHLT 2014

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Vincent Valentine, MD
Links Editor-in-Chief
University of Texas Medical Branch
Galveston, TX, USA

Friday, April 11, 2014

Jason Christie opened the Plenary Sessions for the 34th Annual ISHLT Meeting by "staying classy" in sunny San Diego with the 2014 Program Chair Report. links imageMove over Ron Burgundy. From his report, record breaking attendance with over 3000 attendees and record breaking abstracts with over 1500 submissions and over 1100 (76%) accepted across all categories. Also, there were expanding numbers from "developing nations" which entered the ISHLT from the Middle East, Asia, Eastern Europe and South America. Dr Christie finished his report by pointing out a few innovations ranging from e-Posters, expanded content of Mini-Orals, the OASIS meeting app and a return of the Moderated Poster Sessions to an overview of the content for this year's meeting. The content included World-Class Speakers, Major Clinical Trials and a Thematic structure for the Plenaries. The Pre-meeting and Sunrise Symposia were member submitted and had a cased-based approach of integrating science with patient care with an emphasis on teamwork. For those of you with children or grandchildren, you might note a little wisdom from the Wonder Pets, with the healthy refrain drilled in our future generations, "What's it gonna take?" "Team Work!"

Allan Glanville followed with an eloquent Presidential Address aided by an elephant, sheep, crocodiles, the arbiter bibendi, Woody Guthrie and many apologies. He described the duties of the President to: 1/ Interface with the Community (individuals, advocacy groups, other societies and government organizations), 2/ be the Caretaker of the Future (understand the nature, preserve the fabric and map change through innovation for the ISHLT), links image3/ maintain the tradition of ongoing service and 4/ preserve the Holy Grail of the ISHLT President, that is The Transition, the most important task of handing over the baton.

The elephant metaphor comes from the pachyderm's virtue of memory and patience as well as what's obviously taking up space in the ISHLT. The many elephants in the room this year include: 1/ the ECMO bridge, 2/ Consensus documents, 3/ Advocacy groups, 4/ Donors in China and 5/ CLAD - chronic lung allograft dysfunction. He captured the essence of a herd of sheep by likening them to the ISHLT Board Members or vice versa. He reminded us of the difficult decision goaded by the devil that at times we are "damned if we do" or "damned if we don't" particularly in reference to transplant off ECMO or rather should it be transplant on ECMO. The arbiter bibendi, you know, "the guest of honor whose sole responsibility was to arbitrate the amount of water used to cut the wine," referring to Guidelines within the ISHLT. Dr Glanville further reminds us that Our ISHLT "is made for you and me" and that we are custodians of this land for future generations with reference to Woody Guthrie and Sitting Bull ... YouTube icon This land is your land, this land is our land, this land was made for you and me. His apologies came through a personal glimpse at his career beginning with a snowy summer at the Royal Brompton Hospital in London to Stanford and his final destination at St Vincent's Hospital Darlinghurst with Sanity and Survival. Of course, Allan is referring to "Sanity and Survival, Psychological Aspects of War and Peace" by Jerome D Frank, PhD, MD. Allan asked why are roses at the end of each row of grapevines? I immediately thought, history, tradition and beauty. Then I linked it with the ISHLT and fungi. Roses show the first signs of danger ahead for the grapevines in our wine vineyards, the canary in the mine if you will. Allan concluded that the Presidency is a service position. Further, he cannot think of any other Society that functions as collegially and effectively in governing and directing us than the ISHLT. It was a most humbling pleasure for him to hold this office with special thanks given to those who supported him from the wonderful ISHLT administration, members at large, the Committees, the Councils, his workplace, and in particularly the fortitude and patience of his family. His final points, Dr Glanville is always short on lessons: 1/ Eschew Therapeutic Nihilism - The Lazarus Syndrome, alive and well 12 years later and 2/ in reference to obliterative bronchiolitis and the elephant in the room where it all began for Allan in lung transplantation at Stanford in 1986, "Remember me, Professor Glanville? Stanford 1986. If you're going to shoot at an elephant, Professor Glanville, you better be prepared to finish the job."

Following the President's report we had the Thoracic Registry and MCSD Reports given by Drs Josef Stehlik and Jim Kirklin. links imageDr Stehlik began his report with the near unanimous approval of the new branding of the PowerPoint template and logo for the ISHLT. He showed us successful transplants now populating our registry from Russia, Saudi Arabia, Iran, India, and Korea. The theme from last year's registry report was age, this year's focus is retransplantation. Most adults who undergo heart retransplantation were for CAD and had what appeared to be the best survival curve when compared to those transplanted for cardiomyopathy, primary failure or rejection. In pediatric heart retransplantation, survival was best in those with cardiomyopathy and CAD. In lung transplantation, rates of retransplantation were highest in patients between 18 - 50 years of age, with nearly 1700 retransplants done over two decades and a median survival around 2.5 years. This median survival has been improving with time. Just over 100 retransplants have been performed in the pediatric lung population. Josef finished his report with the regional initiatives of the transplant registry and I2C2 - International and Inter-society Coordination Committee. Turkey and Brazil have been included with registry participation, resources, education and regional outreach.

links imageDr Kirklin began the MCSD report with goals to capture data on implantation and outcomes related to assist devices for use 30 days or more as well as to identify best practices. He pointed out that the IMAC registry is owned by the ISHLT, the actual governance of IMACS is by the IMACS board appointed by the ISHLT leadership, and the ownership of data remains with the submitting hospital. IMACS web based data entry and hospital enrollment went into effect, January 2013. IMACS and Euromacs signed joint agreements for Euromacs to act as a collective and share of information with IMACS in January 2014. Infectious disease variables were programmed into this registry in March 2014. As of 4/1/14, 181 hospitals and nearly 2800 patients have been enrolled representing 22 different countries. Nearly twice as many implants were for destination therapy followed by currently listed bridge to transplant. Two thirds of the patients were under age 65 years with survival rates better in this cohort at around 85% at 1 year. Infection and bleeding are the most common complications at a rate of 6.6 and 6.4 events/100 patient months, respectively. Future tasks include enrolling more hospitals and collectives, finalizing IMACS agreement, securing first Euromacs download, monitoring patient enrollment, distributing reports to hospitals and collectives, and formalizing the committee structure for data access and publications.

An innovating, invigorating, and illuminating presentation on How Digitizing Humans Changes the Future of Medicine delivered by the inimitable invited lecturer, Dr Eric Topol of Scripps Translational Institute went beyond all expectations for the 34th Annual ISHLT. The focus of his talk was on the challenge of caring for the population vs the individual with individualized management from "Prewomb to Tomb." Its essence brought together all innovative strategies from the exposome, epigenome, microbiome, metabolome, proteome, transcriptome, and the genome to imaging, biosensors and social graphing for future decisions in individual patient care. Technology is here with the digital era transforming medicine through metrics potentially measured by wireless devices. His vision of another APP in health care will be called, ADD-APP-TERS. links imageDr Topol shared some examples from the Search Atrial Fibrillation study through iPhone ECG in pharmacies to prevent strokes, comparing 24-hour Holter monitoring with 14-day novel adhesive patch electrocardiographic monitoring, heart failure remote monitoring by measuring thoracic fluid, stroke volume, cardiac output, heart rate, respiratory rate and motion, and the use of edible and embeddable sensors. He referenced his recent JAMA article on how mobile health technologies could change every aspect of health care by delivering better outcomes and lower costs. Real world clinical trial evidence is critically needed for mHealth technologies. Blood coagulation testing using the smartphone touchscreens is here with the Qloudlab involving the smartphone, the cloud and healthcare. With the lab-on-a-chip or lab-in-the-body and better sensors, in the near future patients might present to their healthcare provider when their "check my gallbladder" light comes on. Dr Topol pointed out that today a car has over 400 on-board sensors, a smartphone has more than 10 embedded sensors with four radios, and the human has no sensors. This is going to change. For our heart and lung transplant recipients with the promise and challenge of high-throughput sequencing of the antibody repertoire, it will only be a matter of time we will be able to use universal noninvasive detection of transplant rejection by monitoring donor DNA levels over time, signaling the onset of rejection through shotgun sequencing from cell-free DNA from plasma. Finally, in the age of handheld ultrasound devices, Dr Topol warned to stop listening and look to view this technology as an extension of our senses, predicting a future death of the stethoscope, RIP to the stethoscope 1816-2016, long live the ultrasound, medical imaging and electronic technology. In summary, individualized medicine is upon us from Prewomb to the Tomb with baby planning, undiagnosed diseases, prevention, cancer, molecular diagnosis, longer health spans and the molecular autopsy. With all its promise, it is conceivable that in the future our heads might hang low buried in the many devices and monitors of rapid communication and its shortcuts with texting, tweeting, twittering, instagramming, twirping, and chirping while no one listens and only looks without eye contact, the world could go silent broken only by occasional grunts at each other in a "virtual existence" resembling WALL-E.

links imageSir Terence English ended the first day's Plenary sessions with this year's Lifetime Achievement Award Recipient Lecture: "Follow Your Star." He provided a captivating summary of his illustrious career in a matter of a few moments. From humble beginnings in South Africa he "followed his star" which shimmered like diamonds. In spite of his father's death due to silicosis from working in the mines, Sir Terence studied mining engineering. He worked in Rhodesia as a diamond driller and went on to mining exploration in Quebec and the Yukon. Then a "brighter star" came on the horizon. He started training as a physician at Guy's Hospital in London. His engineering background proved useful in his training for cardiovascular surgery. He went on to perform Britain's first successful heart transplant in 1979 and served as the third ISHLT President from 1984 - 1986. He later published his autobiography, Follow Your Star: From Mining to Heart Transplants - A Surgeon's Story (AuthorHouse, 2011). His message to us today is to remain aware and prepared for a change in direction if a brighter star or "diamond" appears on the horizon during your journey. There are several false starts and mistakes will be made, however along the way embrace these errors, most will provide valuable and enriching experiences.

Saturday, April 12, 2014

Invited lecturer, Dr Lynne Stevenson, kicked off the second day of Plenary Sessions with Trimming Heart Transplantation in the VAD Era. links imageOur Roving Reporters have provided a detailed report of her talk in the article, I Think We Need A Bigger Boat, but I'd like to add to it here. Dr Stevenson closed her presentation with an artistic rendition of the sinking of the Titanic used as a metaphor. The available lifeboats (available donor hearts) fell short in number to evacuate the passengers (the failing hearts) leaving many behind who went down with the ship. The moving and heartfelt centerpiece of this artwork shows an old couple in wheel chairs through the ruptured bow who chose to stay aboard enjoying their last taste of fine wine while listening to the elegant music from the musicians who played on to the end. We refer you to the ISHLT Links April 2012 issue: Titanic, Impact, April, ISHLT. Below are links to the some of the music found in the article:

links image Songe D'Automne
links image My Heart Will Go On
links image Nearer My God To Thee
links image Rose

In keeping with a demand outstripping supply, we tie into the next invited lecturer, Dr Tom Egan who offers a thoughtful and erudite solution through the Frontiers of DCD in Thoracic Transplantation. Dr Egan shows that there is a potentially unlimited supply of lungs for those with lung failure. links imageHe began his presentation with our friendly pig which may either be dinner or a donor? Along with the cartoon of the doctor claiming "he never has any luck with living things" with the dying plants on his desk, Dr Egan proceeds with his proof of concept to use cadaveric lungs as a strategy to increase the donor pool because the lung parenchyma although ischemic is not hypoxic and continues on with cellular respiration for some time after cardiac arrest. With ex-vivo evaluation of human lungs strategies and an ex-vivo CT scan technique as many as 40,000 uncontrolled donations after cardiac death donors (uDCDD) could be found suitable for lung transplantation. He points out that though innovative in some respects today, the first uDCDD was described by Hardy's first case in 1963 and further, until brain death was defined 20 years later, uDCDD were the only donors. Dr Egan did emphasize the many logistical challenges in a process necessary for the desired outcomes. He concluded that there are large numbers suitable for lung recovery with many challenges among which the incidence of both non-pulmonary and pulmonary diseases is higher than anticipated in victims of sudden death and that recovery of organs in uDCDDs is an innovative disruptive technology with logistical obstacles that can be overcome.

The final invited lecturer for the second day of the plenary sessions was given by Alvin Roth of Stanford University entitled Organ Allocation Policy and the Decision to Donate: An Economist's Perspective. Mr Roth posited, how organs are solicited or allocated might influence the supply, by changing donation behavior. He shared with us the editorial about the "Resurrection Men" from the first volume of the Lancet published in 1824 which informs us that the scarcity of deceased donors is older than transplantation. links imageAt that time, there was a need for cadavers to study. This report "... deplores that it is illegal to obtain bodies for dissection, except executed murderers." Also, "the legislature should be entreated to ... devise ... some plan that would make cadavers legally available and which at the same time would not irritate the feelings of those who are naturally prejudiced against dissection."

Dr Roth shared with us the importance of design in securing potential donors during the application of a new or renewal driver's license or ID card. States are beginning to require an "active" or "mandated choice." Moving from an "opt in" to a "mandated choice' as one option. "Don't take 'No' for an answer" is another. He also shared with us Israel's organ allocation of priority categories. The bottom line in the analysis on Israel's organ allocation, priority on organ donor lists provides an incentive to register as a donor. However, with a loophole, this could undermine the benefit of priority. He concluded his talk that priority allocation rules can increase the number of registered donors, by providing an incentive to be an organ donor. The priority system must be well designed. Ask people to become donors more frequently and that mandated choice frames might not generate more donors and might discourage next of kin. Ultimately, the design of the registration and allocation system is vitally important.

Sunday, April 13, 2014

The plenary session lectures on the final day began with Dr Shahid Husain's Consensus Report of the 2014 ISHLT Guidelines for the Management of Fungal Infections in Cardiothoracic Organ Transplant Recipients and Mechanical Circulatory Support (MCS). The most meaningful evidence identifying risk factors for fungal infections (FI) in lung transplantation from several potential risks scored only a moderate in the cystic fibrosis population. links imagePre-transplant colonization, post-transplant colonization, acute rejection with prior colonization, chronic rejection, CMV infection, hypogammaglobulinemia and presence of stent had only low evidence. The risk factors for FI in heart transplantation were reoperation, CMV disease, post-transplant hemodialysis, invasive aspergillosis (IA) in the same heart transplant unit three months before or after the transplantation date. The epidemiologic data of FIs in pediatric lung and heart transplantation are sparse. Regarding the diagnosis of FI serum galactomannan (GM) levels, BAL Aspergillus PCR and serum beta D glucan levels are not recommended, however BAL GM levels for the diagnosis and pre-emptive treatment are recommended with grade 1B and 2D evidence. Prophylaxis and treatment strategies will be forthcoming but the salient features of his overview included: that the optimal duration of antifungal prophylaxis following cardiothoracic transplantation is 4-6 months for universal prophylaxis, or 3-4 months with a pre-emptive strategy. If there is a long-term requirement for prophylaxis (> 6 months) an antifungal agent other than voriconazole is recommended. With treatment, nebulized amphotericin should not be used as the sole therapy for Aspergillus and therapeutic drug monitoring is recommended for azole antifungal agents. For prophylaxis in patient with MCS devices routine perioperative prophylaxis is not recommended but can be considered in those on TPN, known recent colonization with Candida spp from > 2 sites or patients hospitalized on broad spectrum antibiotics > 48 - 72 hours at the time of MCS implantation.

Invited lecturer, Dr Michael Petty, next presented The Invisible Team Member: Family Caregivers of Thoracic Transplantation and Mechanical Circulatory Support Patients. No kin to Tom Petty, but definitely related to potential "heartbreakers," he described that Heart failure patients with poor social support have worse outcomes. links imageLack of social support from a spouse may be worse than lack of social support from others. With Charles Dickens' best of times, despite the difficulties of heart failure, some caregivers express positive effects on their relationship with significant solidarity between themselves and the patient. Lung failure spouses identified benefit in areas or discovering inner strength, support from others and realizing what is important in life. During the worst of times, most difficult tasks for caregivers are related to motivating the heart failure patient to maintain lifestyle changes. Female caregivers demonstrate lower quality of life scores than male caregivers, but the females did demonstrate improved quality of life when involved with care. He provided ten tips for family caregivers which included: 1/ to seek support from other caregivers, they are not alone! 2/ to take care of your own health to be strong enough to care for your loved one. 3/ to accept offers of help. 4/ to learn to communicate effectively with doctors. 5/ that Caregiving requires hard work and requires frequent breaks. 6/ to watch out for depression. 7/ to be open to new technologies to help care for your loved one. 8/ to organize medical information. 9/ to make sure legal documents are in order. 10/ to give yourself credit for doing the best you can in one of the toughest jobs there is!

Within the ISHLT we depend on family caregivers to help our patients to be successful before and after transplantation or implant periods. Family caregivers experience the best and worst of times. Intervention studies are needed rather than observational studies to allow us to address the needs of family caregivers. Long term strategies to support family caregivers are necessary.

The last invited lecturer for the 34th Annual ISHLT meeting and certainly not the least was from our former President Dr Lori West who spoke on Trading Risks of Sensitization in Thoracic Transplantation: ABO-Incompatibility to Achieve HLA-Compatibility? She presented a case of a patient with high class 1 and class 2 calculated PRAs of 98% and 100%, respectively; who would be very unlikely to find a donor. Dr West shared with us the outcomes of ABO-incompatible kidney transplantation in the United States and in Japan. ABO incompatible kidney transplantation accounts for nearly a third of all living donor kidney transplants in Japan with a 9-year graft survival of 83%. Successful experiences of ABO-incompatible adult living donor liver transplantation have been reported with no immunological failure in ten consecutive cases. However, in heart transplantation, unintentional ABO blood group-incompatible (ABOi) transplantation has resulted in poor outcomes with a one year mortality of 32% of 95 identified ABOi transplants. links imageNevertheless, Dr West pointed out the tools of today can allow consideration for planned ABOi transplantation and include: 1/ non-specific immunoadsorption to remove antibodies, 2/ rituximab to deplete rising B cells, 3/ bortezomib to deplete plasma cells, 4/ eculizimab to protect the endothelial surfaces from complement-mediated damage, 5/ antigen-specific antibody immunoadsorption, and 6/ antibody assessment tools. She further pointed out to us the major differences between ABOi heart and ABOi kidney/liver transplantation. First, appropriate typing is needed to avoid antibodies to either donor or recipient: blood products to prime the cardiopulmonary bypass (CPB) circuit, for clinical management and plasma exchange from CPB if necessary. The transfusion medicine and perfusion teams are absolutely necessary. As a result, a recent innovation report in the JHLT from Sweden proved that ABOi heart transplantation can be considered, provided that levels of anti-A and anti-B antibodies are low JHLT 2012;31:1307. Another notable point from Dr West's presentation is that the agglutination assay to describe ABO groups were described in 1900 by Dr Karl Landsteiner, that we use the same technology he used more than a century ago and we monitor and manage incompatible transplant patients with this age-old technology. Today, we can use the microplate hemagglutination assay or iSpot technique. Also, HLA antigens are proteins and ABH antigens are carbohydrates. Red cells express type II-IV, Lewis and sialic acid antigens whereas only type II structures are expressed on vascular endothelium. The heart has fewer cell types of antigens than the kidney and more importantly, IgM antibodies are not the only relevant antibodies. IgG and IgA isotypes are present with IgG and very likely have the greatest impact. Lastly donor-specific antibodies inevitably lead to eventual graft damage, but ABOi grafts are more likely to develop accommodation, because of this, Dr West leaves us with that ABOi heart transplantation should not remain an absolute contraindication for thoracic transplantation in adults.

links imageThe plenary sessions ended with the President's Debate: Stop Treating Secondary Pulmonary Hypertension Right Now! Dr Fernando Torres (PRO) of UT Southwestern pitted against none other than Dr Harrison "Hap" Farber (CON) from Boston University. Though seemingly lopsided with Hap's near undefeated past performances versus Fernando's maiden debate, the odds were certainly stacked against Hap. With an allusion to the upcoming Kentucky Derby, Fernando had a clean start out of the gate with thoughtful and methodical data from a randomized trial published in JAMA showing no support of phosphodiesterase-5 inhibition with sildenafil for 24 weeks in patients in heart failure with preserved ejection fractions and from ARIES-3, definitive conclusions about safety and efficacy in patients with non-Group 1 pulmonary hypertension cannot be made on the use of ambrisentan. In the back stretch and around the final turn, Dr Torres had widened his lead.

Then, not to be out done, Hap opened his con argument in the final moments with ... "Things aren't always what they seem!" The audience was instructed to close their eyes and listen to AC/DC's YouTube icon Highway to Hell (performed by 2Cellos). As the debaters approached the finish line, Hap was closing in fast on Fernando's commanding lead. Hap acknowledged no data to support the use of pulmonary hypertension therapies in patients with PH related to left heart disease. links imageHowever, he turned to the individual patient, then Hap poured it on, evoking Dr Topol's presentation about individualization, as he presented a 63-year-old hypertensive, diabetic dyslipidemic male with obstructive sleep apnea on CPAP who presented with progressive dyspnea on exertion. The ECHO showed normal LV size, with 35-40% LVEF, normal LV diastolic relaxation, normal LA and mild right atrial enlargement. There was flattening of the interventricular septum consistent with RV pressure and volume overload with a dilated IVC and an estimated pulmonary artery pressure of 85 mm Hg. Rest of his workup revealed no clots, normal PFTs and negative serologies. RHC showed RVP of 70/3, PAP 72/34, PCWP 13 and a CI of 1.2. Epoprostenol was started with slow titration. One year later, the patient's PVR dropped nearly 36%, cardiac output improved by 67% and he became a functional class II patient. Four years later, his daughter was diagnosed with pulmonary arterial hypertension with the same BMPR2 mutation found in him. As the two debaters crossed the finish line, the photo finish confirmed a dead heat! In summary, stop thinking you can never treat, evoking Dr Glanville's advice to "eschew therapeutic nihilism", start thinking outside the box! And look at each patient individually and as an individual human!

Disclosure Statement: the author has no conflicts of interest to report.

Photos courtesy of www.karrasphoto.com

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