Urgent Transplantation Research Articles

Predictive Ability of Cardiopulmonary Exercise Test Parameters in Heart Failure Patients with Cardiac Resynchronization Therapy.

ResumoFundamento Há evidências sugerindo que um corte do pico de consumo de oxigênio (pVO2) de 10ml/kg/min fornece uma estratificação de risco mais precisa em pacientes com Terapia de Ressincronização Cardíaca (TRC).Objetivo Comparar o poder prognóstico de vários parâmetros do teste cardiopulmonar de exercício (TCPE) nesta população e avaliar a capacidade discriminativa dos valores de corte de pVO2 recomendados pelas diretrizes.Métodos Avaliação prospectiva de uma série consecutiva de pacientes com insuficiência cardíaca (IC) com fração de ejeção do ventrículo esquerdo ≤40%. O desfecho primário foi um composto de morte cardíaca e transplante cardíaco urgente (TC) nos primeiros 24 meses de acompanhamento, e foi analisado por vários parâmetros do TCPE para a maior área sob a curva (AUC) no grupo TRC. Uma análise de sobrevida foi realizada para avaliar a estratificação de risco fornecida por vários pontos de corte diferentes. Valores de p < 0,05 foram considerados significativos.Resultados Um total de 450 pacientes com IC, dos quais 114 possuíam aparelho de TRC. Esses pacientes apresentaram um perfil de risco basal mais alto, mas não houve diferença em relação ao desfecho primário (13,2% vs 11,6%, p = 0,660). A pressão expiratória de dióxido de carbono no limiar anaeróbico (PETCO2AT) teve o maior valor de AUC, que foi significativamente maior do que o de pVO2 no grupo TRC (0,951 vs 0,778, p = 0,046). O valor de corte de pVO2 atualmente recomendado forneceu uma estratificação de risco precisa nesse cenário (p <0,001), e o valor de corte sugerido de 10 ml/min/kg não melhorou a discriminação de risco em pacientes com dispositivos (p = 0,772).Conclusão A PETCO2AT pode superar o poder prognóstico do pVO2 para eventos adversos em pacientes com TRC. O ponto de corte de pVO2 recomendado pelas diretrizes atuais pode estratificar precisamente o risco dessa população.

COVID-19 as a putative trigger of anti-MDA5-associated dermatomyositis with acute respiratory distress syndrome (ARDS) requiring lung transplantation, a case report

BackgroundAutoimmune disease following COVID-19 has been studied intensely since the beginning of the pandemic. Growing evidence indicates that SARS-CoV-2 infection, by virtue of molecular mimicry can lead to an antigen-mediated cross-reaction promoting the development of a plethora of autoimmune spectrum diseases involving lungs and extrapulmonary tissues alike. In both COVID-19 and autoimmune disease, the immune self-tolerance breaks, leading to an overreaction of the immune system with production of a variety of autoantibodies, sharing similarities in clinical manifestation, laboratory, imaging, and pathology findings. Anti-Melanoma Differentiation-Associated gene 5 dermatomyositis (anti-MDA5 DM) comprises a rare subtype of systemic inflammatory myopathies associated with characteristic cutaneous features and life-threatening rapidly progressive interstitial lung disease (RP-ILD). The production of anti-MDA5 autoantibodies was proposed to be triggered by viral infections.Case presentationA 20-year-old male patient with polyarthritis, fatigue and exertional dyspnea was referred to our department. An elevated anti-MDA5 autoantibody titer, myositis on MRI, ground glass opacifications on lung CT and histological features of Wong-type dermatomyositis were confirmed, suggesting the diagnosis of an anti-MDA5 DM. Amid further diagnostic procedures, a serologic proof of a recent SARS-CoV-2 infection emerged. Subsequently, the patient deteriorated into a fulminant respiratory failure and an urgent lung transplantation was performed, leading to remission ever since (i.e. 12 months as of now).ConclusionsWe report a unique case of a patient with a new-onset anti-MDA5 DM with fulminant ARDS emerging in a post-infectious stage of COVID-19, who underwent a successful lung transplantation and achieved remission. Given the high mortality of anti-MDA5 DM associated RP-ILD, we would like to highlight that the timely recognition of this condition and urgent therapy initiation are of utmost importance.

The prognostic value of the cardiorespiratory optimal point during submaximal exercise testing in heart failure

IntroductionPeak oxygen consumption (pVO2) is a key parameter for assessing the prognosis of heart failure with reduced ejection fraction (HFrEF). However, it is less reliable when the cardiopulmonary exercise test (CPET) is not maximal. ObjectiveTo compare the prognostic power of various exercise parameters in submaximal CPET. MethodsAdult patients with HFrEF undergoing CPET in a tertiary center were prospectively assessed. Submaximal CPET was defined as a respiratory exchange ratio ≤1.10. Patients were followed for one year for the primary endpoint of cardiac death and urgent heart transplantation (HT). Various CPET parameters were analyzed as potential predictors of the combined endpoint and their prognostic power (area under the curve [AUC]) was compared using the Hanley-McNeil test. ResultsCPET was performed in 442 HFrEF patients (mean age 56±12 years, 80% male), of whom 290 (66%) had a submaximal CPET. Seventeen patients (6%) reached the primary endpoint. The cardiorespiratory optimal point (COP) had the highest AUC value (0.989, p<0.001), and significantly higher prognostic power than other tested parameters, with pVO2 presenting an AUC of 0.753 (p=0.001). COP ≥36 had significantly lower survival free of HT during follow-up (p<0.001) and presented a sensitivity of 100% and a specificity of 89% for the primary endpoint. ConclusionCOP had the highest prognostic power of all parameters analyzed in a submaximal CPET. This parameter can help stratify HFrEF patients who are physiologically unable to reach a maximal level of exercise.

Prognosis value of Forrester's classification in advanced heart failure patients awaiting heart transplantation.

The value of Forrester's perfusion/congestion profiles assessed by invasive catheter evaluation in non-inotrope advanced heart failure patients listed for heart transplant (HT) is unclear. We aimed to assess the value of haemodynamic evaluation according to Forrester's profiles to predict events on the HT waitlist. All non-inotrope patients (n=837, 79% ambulatory at listing) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 with right heart catheterization (RHC) were included. The primary outcome was a combined criteria of waitlist death, delisting for aggravation, urgent HT or left ventricular assist device implantation. Secondary outcome was waitlist death. The 'warm-dry', 'cold-dry', 'warm-wet', and 'cold-wet' profiles represented 27%, 18%, 27%, and 28% of patients, respectively. At 12months, the respective rates of primary outcome were 15%, 17%, 25%, and 29% (P=0.008). Taking the 'warm-dry' category as reference, a significant increase in the risk of primary outcome was observed only in the 'wet' categories, irrespectively of 'warm/cold' status: hazard ratios, 1.50; 1.06-2.13; P=0.024 in 'warm-wet' and 1.77; 1. 25-2.49; P=0.001 in 'cold-wet'. Haemodynamic assessment of advanced HF patients using perfusion/congestion profiles predicts the risk of the combine endpoint of waitlist death, delisting for aggravation, urgent heart transplantation, or left ventricular assist device implantation. 'Wet' patients had the worst prognosis, independently of perfusion status, thus placing special emphasis on the cardinal prominence of persistent congestion in advanced HF.

Registro español de trasplante cardiaco. XXXIII informe oficial de la Asociación de Insuficiencia Cardiaca de la Sociedad Española de Cardiología

Introduction and objectivesThis report updates the annual data of the Spanish heart transplant registry with the procedures performed in 2021. MethodsWe describe the clinical profile, therapeutic characteristics and outcomes in terms of survival of the procedures performed in 2021. Their temporal trends are updated for the 2012 to 2020 period. ResultsIn 2021, 302 heart transplants were performed (8.6% increase versus 2020). The tendency in 2021 confirmed that of prior years, with fewer urgent transplants and a preference for the use of ventricular assist devices. The remaining characteristics and survival showed a clear trend toward stability in the last decade. Compared with 2019, the SARS-CoV-2 pandemic (2020 and 2021) did not affect short- or long-term survival. ConclusionsIn 2021, transplant activity returned to prepandemic levels. The SARS-CoV-2 pandemic did not significantly affect transplant outcomes. The main transplant features and outcomes have clearly stabilized in the last decade.

Pick Your Threshold: A Comparison Among Different Methods of Anaerobic Threshold Evaluation in Heart Failure Prognostic Assessment

In clinical practice, anaerobic threshold (AT) is used to guide training and rehabilitation programs, to define risk of major thoracic or abdominal surgery, and to assess prognosis in heart failure (HF). AT of oxygen uptake (V.O2; V.O2AT) has been reported as an absolute value (V.O2ATabs), as a percentage of predicted peak V.O2 (V.O2AT%peak_pred), or as a percentage of observed peak V.O2 (V.O2AT%peak_obs). A direct comparison of the prognostic power among these different ways to report AT is missing. What is the prognostic power of these different ways to report AT? In this observational cohort study, we screened data of 7,746 patients with HF with a history of reduced ejection fraction (< 40%) recruited between 1998 and 2020 and enrolled in the Metabolic Exercise Combined With Cardiac and Kidney Indexes register. All patients underwent a maximum cardiopulmonary exercise test, executed using a ramp protocol on an electronically braked cycle ergometer. This study considered 6,157 patients with HF with identified AT. Follow-up was median, 4.2 years (25th-75th percentiles, 1.9-5.0 years). Both V.O2ATabs (mean ± SD, 823 ± 305mL/min) and V.O2AT%peak_pred (mean ± SD, 39.6 ± 13.9%), but not V.O2AT%peak_obs (mean ± SD, 69.2 ± 17.7%), well stratified the population regarding prognosis (composite end point: cardiovascular death, urgent heart transplant, or left ventricular assist device). Comparing area under the receiver operating characteristic curve (AUC) values, V.O2ATabs (0.680) and V.O2AT%peak_pred (0.688) performed similarly, whereas V.O2AT%peak_obs (0.538) was significantly weaker (P< .001). Moreover, the V.O2AT%peak_pred AUC value was the only one performing as well as the AUC based on peak V.O2 (0.710), with an even a higher AUC (0.637 vs0.618, respectively) in the group with severe HF (peak V.O2< 12mL/min/kg). Finally, the combination of V.O2AT%peak_pred with peak V.O2 and V. per CO2 production shows the highest prognostic power. In HF, V.O2AT%peak_pred is the best way to report V.O2 at AT in relationship to prognosis, with a prognostic power comparable to that of peak V.O2 and, remarkably, in patients with severe HF.

Transhepatic double lumen hemodialysis catheter in exhausted vascular access: Feasibility, functionality, and outcome among hemodialysis patients.

Permanent arteriovenous fistula and graft are considered the best options for hemodialysis in end-stage renal disease patients. Temporary access using the internal jugular or femoral veins is the feasible option in acute cases of dialysis and if permanent access is unavailable. Occasionally, however, these access sites are unusable after consecutive blockage of the upper and lower extremities veins. A transhepatic or translumbar approach might be the only unconventional way to ensure a sufficient blood flow for adequate dialysis. Retrospective data on all transhepatic catheters (THCs) in patients at the King Faisal Specialist Hospital and Research Center in Jeddah, Saudi Arabia were collected. The catheters were inserted over a 10-year period (2009-2019). A minimum of 1 year of follow-up from the last catheter insertion was considered for analysis. A total of 12 patients had THCs with a mean age of 42.5 ± 12.2 and pre-insertion mean dialysis duration of 130.0 ± 72.9 months. All catheters were functional from the start with no immediate complications. A total of 35 catheter replacements over guidewires were made with a median of 2.0 catheters (range of 0-10). The mean blood flow was 300 ± 30 ml/minute with a mean Kt/v of 1.4 ± 0.4. The median initial (primary) device service interval was 68 (range 6-1531 days) and the median total access site service interval was 392 (range 76-2698 days). Catheter complications included catheter migration, thrombosis, and bloodstream infection occurring at a rate of 0.12, 0.18, and 0.046 per 100 catheter days respectively. Transhepatic catheters provide safe, feasible access in patients with exhausted vascular access. Patients who undergo THC insertion should be worked up for innovative permanent vascular access or urgent transplantation utilizing unconventional vascular techniques to avoid death due to lack of access.

Prognostic value of 6-min walk test compared to cardiopulmonary exercise test in patients with severe heart failure.

The 6-min walk test (6MWT) and cardiopulmonary exercise test (CPET) are both predictive in heart failure (HFrEF). Although 6MWT substitutes for CPET in HFrEF patients, as submaximal testing may be preferable, its prognostic superiority still needs to be verified, particularly in regard to beta blockers (BBs). We aimed to compare the prognostic role of CPET and 6MWT and investigate whether BB therapy influences the predictive value. This is a single-center, retrospective study. Advanced HFrEF patients were followed up for 3 years: events were cardiovascular death or urgent heart transplantation. We analyzed the predictive capacity of CPET and 6MWT in patients, and subdivided according to use of BBs. In a group of 251 HFrEF patients, we found a correlation between meters and peak VO2 (r2 = 0.94). Over the 3-year follow-up, 74 events were recorded. Both CPET and 6MWT variables were correlated with outcome at univariate analysis (meter and VE/VCO2 slope, peak VO2, VO2 at ventilatory anaerobic threshold, percentage predicted of peak VO2), but only percentage predicted of peak VO2 (pppVO2) was an independent predictor. In 103 HFrEF patients on BBs (23 nonsurvivors), neither pppVO2 nor meter were predictive, while in 148 patients not treated with BB (51 with events) pppVO2 was selected as an independent prognostic parameter (P = 0.001). 6MWT is a valid alternative to CPET, although the percentage of predicted of peak VO2 emerged as the strongest predictor. Nonetheless, our results suggest that both functional derived parameters are not predictive among those patients treated with BBs. Further studies are necessary to confirm these findings.

C73 PICK YOUR THRESHOLD! HOW TO CALCULATE THE ANAEROBIC THRESHOLD TO STRATIFY HEART FAILURE PROGNOSIS: A COMPARISON BETWEEN ABSOLUTE VALUE, PERCENTAGE OF PEAK VO2 OR PERCENTAGE OF PREDICTED MAXIMUM VO2 IN A LARGE MULTICENTER COHORT OF HFREF PATIENTS WHO UNDER

Abstract Background The anaerobic threshold (AT), identifies the moment during a maximal exercise when hyperventilation occurs in response to the introduction of an anaerobic metabolism. Its value is indicative of the subject‘s training and/or health, it can be used to guide training, rehabilitation or to define appropriateness to undergo major thoracic or abdominal surgery, and it is related to heart failure (HF) prognosis. AT can be expressed as absolute value or as the percentage of predicted maximum VO2 (VO2AT%pred). However, it is not uncommon to find papers that refer AT to the peak VO2 value achieved (VO2AT%peak), rather than its predicted value, but a direct comparison of the prognostic power of these different variables is missing. In this work, we aim to compare the risk–identifying ability of the AT value when expressed in these three different ways in a large population of HF patients. This will help identify which is more correct to use in assessing patient prognosis, especially when peakVO2 is not reached appropriately. Methods The population analyzed counts 7746 patients with HF with history of reduced EF (&amp;lt;40%), recruited between 1998 and 2020 within the MECKI score project. All patients underwent a maximal cardiopulmonary exercise test (CPET), executed in using a ramp protocol on an electronically braked cycle ergometer. Results The present study considered 6157 HF patients with identified AT during the CPET, with a median follow up of 1528 days (689–1826). The main characteristics are reported in Figure 1. Figure 2 shows stratification of patients according to these 3 variables divided in tertiles, considering cardiovascular death (combination of cardiovascular death, urgent transplant or LVAD implantation) as an end point. Comparing the AUC of the three variables considered, we found similar values between VO2AT and VO2AT%pred, while the peak VO2AT% value was significantly lower (p &amp;lt; 0.001), as shown in Figure 3A. Moreover VO2AT%pred is the only variable to maintain a comparable ROC to the peakVO2 one, with the others being significantly lower (Figure 3B). Conclusions VO2 at AT should always be expressed as % of predicted maximal VO2 to be reliable in predicting prognosis in HF patients. Moreover, evaluating a sub–maximal exercise, VO2AT%pred is the only variable to maintain a comparable prognostic power to the peakVO2 one.

P251 PERIODIC BREATHING (EOV) ON CARDIORESPIRATORY STRESS TESTING: ARE THERE PROGNOSTIC DIFFERENCES BETWEEN PATIENTS WITH PERIODIC BREATHING THAT PERSISTS THROUGHOUT THE TEST AND PATIENTS TO WHOM IT DISAPPEARS?

Abstract Introduction Oscillatory exercise ventilation (EOV) is frequently seen in patients with severe heart failure (HF) and has a ne:gative prognostic value in both patients with reduced HF and those with average ejection fraction. Two types of EOV have been described one that lasts throughout exercise and one that disappears before the end of exercise, Figure 1 Aim of the Study It is currently unknown whether there are differences in prognosis and functional capacity between HF patients with EOV that persists or disappears during exercise. Population Male and female patients, aged≥18 years, diagnosed with HF and LVEF&amp;lt;45% were enrolled. Methods The retrospective study enrolled patients who performed a cardiopulmonary exercise test (CPET) and presented with EOV during exercise (Monzino Heart Center Laboratory and patients included in the MECKI score registry, identified a total of 255 patients). A subset of 100 patients underwent measurement of maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) before and after exercise (Table 2). All patients were treated at the top of therapy for HF. CPETs were performed and analyzed with a standard approach using a customized ramp protocol. The main parameters obtained are reported and compared in Table 1. EOV was defined according to as a cyclic fluctuation in ventilation as proposed by Corrà et al. Statistical analysis:Data are reported as mean ± standard deviation or median and interquartile range as appropriate. The two groups of patients were compared by t test for unpaired data in the case of data with normal distribution. Mortality was analyzed by Kaplan Meier curves and Log Rank test. Survival was considered using the composite end–point of cardiovascular death, urgent cardiac transplantation, or implantation of a left ventricular assist device. The median MECKI score of the total population was 5.5% (2.5–13.7) with no significant differences between the 2 groups. Figure 1 shows the Kaplan Meyer describing the 5–year survival analysis in both groups. Conclusions Patients with disappearing EOV demonstrated better exercise performance but no significant difference in survival and major prognostic parameters.

P36 THE ELDEST HEART TRANSPLANTED PATIENT IN EUROPE: 36 YEARS SURVIVAL AND STILL GOING ON

Development of endomyocardial biopsy for acute rejection monitoring in the early Seventies, and above all use of cyclosporine in the clinical practice starting from 1980, introduced the modern era of heart transplantation. Following the initial positive outcomes, the first Italian transplant was performed in Padua by V.Gallucci on November 15th 1985. This pioneering success was rapidly repeated in Pavia, where M.Viganò performed the second transplant on Novembre 17th. Recipient was 20 years old man, suffering from dilated cardiomyopathy, on urgent transplant list. Cardiac index was 1.38 l/min/m2 and pulmonary vascular resistance 1.6 WU. Donor was a 14 years old boy died of brain injury. Total ischemic time was 125 minutes. Induction immunosuppression consisted of horse anti–lymphocyte immunoglobulins, whereas maintenance therapy included cyclosporine, azathioprine and steroids. Postoperative course was complicated by pericardial effusion and cholestatic jaundice. Later pulmonary aspergillosis occurred and due to the profound immunodepression was complicated by fungal localization at L2 vertebral body. The infection was treated with surgical removal of the secondary localization and amphotericin B administration. On December 6th severe acute rejection was found at biopsy and treated with i.v. steroid pulse. Length of ICU and hospital stay was 28 and 72 days, respectively. In 1998 HCV infection was detected and eradicated in 2017 with elbasvir/grazoprevir therapy. Complications of long term immunosuppressive treatment included dyslipidemia, myeloma and basal cell carcinoma. Due to long–term calcineurin inhibitors therapy progressive chronic renal failure occurred, leading to replacement therapy in 2015 and kidney transplantation in 2016. In 2015 the patient underwent percutaneous coronary intervention with stents implantation in two marginal branches and in the anterior descending artery in 2021. Everolimus was introduced to slow down progression of cardiac allograft vasculopathy. In 2020 he suffered from Covid–19, but the course of infection was uneventful being cough the only symptom. We report the eldest survivor after heart transplant in Europe. Our case demonstrates that despite early and long–term complications of immunosuppressive therapy, a careful and patient tailored management allowed an amazing outcome. Nowadays heart transplant remains the best treatment for end stage heart failure and allows to resume a nearly normal quality of life.

Salvage Liver Transplant in the Treatment of a Child With Local Recurrence of Hepatoblastoma

Hepatoblastoma is the most common primary liver cancer of childhood, accounting for two-thirds of primary malignant hepatic neoplasms. Radical surgical removal combined with efficient chemotherapy is essential for cure. Despite a complete tumor resection, hepatoblastoma may recur as isolated local disease. Intrahepatic recurrence of hepatoblastoma after liver resection is among the indications for liver transplant. Here, we present a patient who underwent salvage liver transplant for the treatment of local recurrence of hepatoblastoma. A 13-year-old boy who was diagnosed with hepatocellular carcinoma arising from the left liver lobe and who had been treated with surgical resection was admitted to our outpatient oncology clinic for further evaluation because alpha-fetoprotein levels had started to increase after surgery. Histopathological reexamination of hemihepatectomy material showed a histological aspect of an epithelial hepatoblastoma. Magnetic resonance imaging revealed multifocal lesions in the right liver lobe compatible with local recurrence. Despite a favorable initial response to chemotherapy, the tumor showed progression with increased alpha-fetoprotein levels. The patient was deemed a viable candidate for an urgent liver transplant and underwent right lobe living donor liver transplant. He had excellent graft function without any complications or signs of malignancy in the last follow-up visit at 7 months posttransplant. Salvage liver transplant is a lifesaving and sometimes the only treatment option for patients with local recurrence of hepatoblastoma. Although transplant in the salvage setting has been associated with worse outcomes than primary transplant, recent data have indicated more favorable and acceptable outcomes. Further studies are warranted to better understand the role of salvage liver transplant in the treatment of hepatoblastoma. Early consultation with the liver transplant team is critical in children who are most likely to need extreme resection or liver transplant.

Distribution of amanitine-containing macromycetes in the territory of Russia

Introduction. The toxic effect of amanitin-containing macromycetes, or phalloidin syndrome, is accompanied by low patient survival and it remains as one of the leading causes of urgent liver transplantation. As a result, the problems of biodiversity and the distribution of amanitin-containing fungi leading to this condition appear in a relevant light for toxicology. Materials and methods. The study was carried out in two stages. At the first stage, a preliminary list of amanitin-containing macromycetes was compiled by means of a system search in the PubMed database. At the second stage of the study, the presence and occurrence of amanitin-containing taxa in Russia were analyzed. Results. Based on the literature sources and data of the Laboratory of Geography and Systematics of Fungi of the Komarov Botanical Institute of the Russian Academy of Sciences, maps of the administrative-territorial occurrences in Russia of twenty-one species of amanitin-containing macromycetes were compiled: five of Amanita, one of Galerina and fifteen of Lepiota. The species concepts of some poisonous taxa and their key identification features were reviewed. The debatable ideas about the toxicity of two Conocybe species are highlighted. Limitations. The study takes into account only the specific occurrence of poisonous fungi in various territories of Russia, without considering the density and frequency of their growth, which may make it difficult to assess the relationship between the data presented and the likelihood of poisoning by the species in question in individual administrative units. Conclusion. As a result of the study, the boundaries of the distribution of poisonous fly agaric and Galerina species were identified, as well as the territories with the highest registered diversity of Lepiota: the Moscow Region and the Primorsky Territory.

Cystatin C- versus Creatinine-Based Assessment of Kidney Function in Advanced Heart Failure: Insights from REVIVAL

<h3>Purpose</h3> Advanced heart failure (AHF) is associated with muscle wasting, potentially leading to overestimation of kidney function using serum creatinine (sCr)-based estimated glomerular filtration rate (eGFRsCr). Since cystatin C (CysC)-based eGFR (eGFRCysC) is less influenced by muscle mass, higher eGFRsCr in relation to eGFRCysC may reflect sarcopenia. In a cohort of AHF pts, we investigated the association of eGFRCysC and eGFRsCr with a composite endpoint of ventricular assist device (VAD), urgent transplant, or death. We hypothesized that surrogates of sarcopenia (i.e. lower handgrip strength [HGS] and reduced functional capacity) would be associated with the difference between eGFRCysC and eGFRCr (eGFRdiff). <h3>Methods</h3> Among 400 pts enrolled in REVIVAL (Registry Evaluation of Vital Information for VAD in Ambulatory Life), 270 had concomitant CysC and sCr measures. eGFRdiff was calculated as eGFRCysC - eGFRsCr. HGS, peak oxygen consumption (VO2 max) and 6-minute walk test distance (6MWTd) were concurrently assessed. <h3>Results</h3> eGFRCysC reclassified 57% of the pts to different GFR categories and resulted in a higher prevalence of severe kidney dysfunction (Figure A). In adjusted models, for each standard deviation decrease in HGS, VO2 max and 6MWTd, eGFRdiff changed by -8, -3 and -3 ml/min/1.73m², respectively (all p<0.03). eGFRCysC had a stronger association with the composite endpoint than eGFRsCr (adjusted hazard ratio [aHR]: eGFRCysC 1.35, p=0.025; eGFRsCr: 1.18, p=0.23). Pts reclassified to more advanced kidney dysfunction when using eGFRCysC had an increased risk for the composite endpoint (aHR 1.82, p=0.006; Figure B). <h3>Conclusion</h3> In AHF pts, when compared with sCr, CysC strengthens the association between kidney function and a composite of VAD, urgent transplant, or death. Lower HGS and reduced functional capacity are associated with higher eGFRsCr in relation to eGFRCysC, suggesting that sCr-based assessment may overestimate kidney function in AHF pts with sarcopenia.

Risk Stratification in Patients with Pulmonary Arterial Hypertension and Candidates for Lung or Heart-Lung Transplantation

<h3>Purpose</h3> During the 2018 6^th PH World Symposium, it was stated that risk stratification scores may be used for the decision of lung (LT) or heart-lung transplantation (HLT) listing in patients with pulmonary arterial hypertension (PAH). The objective of our study was to evaluate risk assessment tools in a cohort of PAH patients listed for LT or HLT. <h3>Methods</h3> All PAH patients listed for LT or HLT between 01/2006 and 12/2018 were included excepted patients with pulmonary veno-occlusive disease or congenital heart diseases because of the specific indications for transplantation in these subtypes of PAH. At the time of listing, risk stratification was assessed according to the ESC-ERS criteria (invasive French and COMPERA methods) and the REVEAL Lite score. The primary endpoint was overall survival after listing. Secondary outcome measures were mortality on waiting list, post-transplant survival, and cumulative incidence of chronic graft dysfunction. <h3>Results</h3> One hundred and six PAH patients were listed for LT or HLT between 01/2006 and 12/2018. The mean age was 37±12 years (73% females). Proportion of idiopathic/heritable PAH was 88%. Overall survival after listing was 72%, 62% and 58% at 1, 3 and 5 years respectively. It was significantly lower in "high risk" patients according to the French method (p=0.0004), the COMPERA method (p=0.005), and the REVEAL Lite score (p=0.01). The mortality rate on list was higher in the "high risk" patients (from 17% with the French method to 19% with the COMPERA method) and urgent transplantation was more frequently performed. Post-transplant survival was 81%, 71% and 66% at 1, 3 and 5 years respectively. It was significantly lower in "high risk" patients without difference in cumulative incidence of chronic graft dysfunction. <h3>Conclusion</h3> PAH patients classified as "high risk" at the time of listing for LT or HLT have poorer outcomes. Time for listing should be anticipated and "high risk" patients should be prioritized to reduce waiting list mortality and improve post-transplant outcomes.

Comparison of Outcomes Following Physician Directed Bolus vs. Strict Infusion Protocol of Tissue Plasminogen Activator for Thrombolytic Treatment of Pump Thrombosis

<h3>Purpose</h3> There is a lack of consistent approach to pump thrombosis (PT) in ventricular assist device (VAD) supported patients. Previously, bolus thrombolysis was administered at physicians' discretion, guided by changes in pump parameters. More recently, we adopted a strict protocol with invasive haemodynamic monitoring to target mean arterial pressure <80mmHg and continuous infusion of tissue plasminogen activator (tPA) to achieve sustained normalisation of pump flow and power derivatives. We compare outcomes following bolus protocol (BP) and strict infusion protocol (SIP). <h3>Methods</h3> Single-centre retrospective analysis of all patients treated with thrombolysis for VAD PT between 2007-2020. Patients divided into two cohorts (BP and SIP) based on PT treatment. Baseline demographics, antithrombotic therapy, pump parameters and biochemistry were collected prior to PT event, at diagnosis and following thrombolysis. Outcomes reported included need for repeated thrombolysis doses, post thrombolysis major bleeding and death, and survival to transplant. <h3>Results</h3> Mean age 51.7y, 23.5% female. All supported with Medtronic HVAD. 21 PT events in 17 patients; 10 patients with 11 cases in BP group, 7 patients with 10 cases in SIP group. SIP group had more pre-implant renal dysfunction (mean GFR 54 vs. 81ml/min/1.73m2, p=0.017), and lower stable post-implant MAP (mean 72 vs. 76, p=0.05). Repeated thrombolytic doses were never required following SIP vs. 70% following BP (p=0.01). No patients required pump exchange, however 1 in each group required urgent heart transplant listing. Numerically fewer post thrombolysis major bleeds (2 vs. 3) and deaths (0 vs. 3) following SIP compared with BP. All SIP patients survived to transplant, compared with 70% of BP patients(figure 1). <h3>Conclusion</h3> SIP is safe for treatment of PT in VAD supported patients, with excellent associated survival to transplant, and trend towards improved post-thrombolysis outcomes.

A Multi-Center Evaluation of Outflow Graft Obstruction with a Fully Magnetically Levitated Left Ventricular Assist Device

<h3>Purpose</h3> The HeartMate3 (HM3) left ventricular assist device (LVAD) has markedly improved hemocompatibility related adverse outcomes. In sporadic cases, external compression of the outflow graft causing obstruction (eOGO) can result from gelatinous substance accumulation between outflow graft and its bend relief covering. We sought to evaluate the prevalence, temporal course and clinical implications of eOGO with the HM3 LVAD in a global cohort study. <h3>Methods</h3> A Multi-center retrospective analysis was conducted among 2014 HM3 LVAD patients across 16 cardiac centers in 8 countries (between 11/2014 and 4/2021). Presence of eOGO was defined as >25% of cross-sectional area identified by established imaging (percutaneous angiography, computed tomography or intravascular ultrasound). The prevalence and annual incidence were calculated. Serious adverse events and outcome (death, transplant or device exchange) at the end of the study were analyzed for those eOGO cases that required therapy versus those who were observed. <h3>Endpoints</h3> Among 2014 patients, 61 patients were diagnosed with eOGO at a median LVAD support duration of 1024 [IQR: 636-1409] days. The overall prevalence of eOGO was at 3.0 %. The incidence at 1, 2, 3, 4, and 5 years on support was 0.6, 2.8, 4.1, 4.6 and 9.8 %. Of 52 patients, who required a therapeutic intervention, 26 underwent surgical revision, 16 patients were treated by percutaneous stent implantation, 8 underwent urgent heart transplantation and 2 died before intervention. In 9 patients a watchful waiting strategy without treatment was chosen. The mortality among those requiring therapeutic intervention was 9 of 52 (17.3%). This global multicenter cohort study suggests that while rare, HM3 LVAD supported patients may develop eOGO with an increasing incidence after 1 year on support. While targeted engineering efforts to alleviate this complication are underway by addressing early detection as well as outflow graft and bend relief design, clinicians must remain vigilant to this complication, especially in long-term survivors supported with the HM3 LVAD.

Predictive Role of Soluble ST2 in Patients on Left Ventricular Assist Device Support

<h3>Purpose</h3> Soluble suppression of tumorigenicity-2 (sST2) is a prognostic indicator for mortality in heart failure (HF) patients and therefore a valuable tool in risk stratification. After implantation of a continuous flow left ventricular assist device (cf-LVAD), sST2 levels drop significantly. Whether sST2 levels are predictive of adverse outcome in patients on LVAD support remains unknown. We hypothesized that elevated sST2 predict mortality in LVAD patients. <h3>Methods</h3> Between March 2006 and July 2021, 422 patients were primarily implanted with a HeartMate II, HeartMate 3 or HeartWare LVAD in a single centre. sST2 was measured during regular outpatient visits and from biobanked samples if available. All sST2 measurements of these patients until July 2021 were retrieved. Time varying covariate cox regression was used to estimate the effect of sST2 on the primary outcome, stratified for device type and adjusted for the pre-operative variables age, sex, temporary support at implantation, INTERMACS 1 status and ischemic etiology. Primary outcome was death or urgent heart transplant (HTx) and patients were censored if they were explanted, received non-urgent HTx, or for ongoing support at the end of the follow-up. <h3>Results</h3> Post-operative sST2 measurements of 252 LVAD patients were included for analysis, of which 29%, 23%, and 48% received a HeartWare, HeartMate II or HeartMate 3, respectively. The median age was 55 and 64% were male. Median follow-up time was 899 days, during which 35 patients died, 12 patients received urgent HTx and 31 patients received HTx after normal listing. In total, 1475 post-operative sST2 measurements were used for analysis, with a median of 28.2 ng/ml (inter quartile range: 20.8 ng/ml). The multivariate adjusted time dependent cox model resulted in a HR of 1.02, with p<0.001 for sST2. <h3>Conclusion</h3> sST2 is predictive for all-cause mortality in patients on LVAD support. Therefore, a closer follow-up may be recommended in patients with high sST2 measures. In addition, further research is warranted into the mechanisms of elevated sST2 in LVAD patients and possible targeted interventions to improve prognosis.

The Devil is in the Details: A Case of Fulminant Giant Cell Myocarditis

<h3>Introduction</h3> Giant cell myocarditis is a rare, rapidly progressive disease that requires a high degree of clinical suspicion. We report a case of fulminant giant cell myocarditis with profound cardiogenic shock requiring mechanical circulatory support and ultimately, successful heart transplant. <h3>Case Report</h3> A 53-year-old female with 11 prior pregnancies presented with chest pain and was found to have complete heart block and presumed NSTEMI with troponin-I of 6 ng/mL. Coronary angiogram revealed 85% stenosis of the right coronary artery which was stented, and a pacemaker was implanted for complete heart block; EF was 50% at that time. She was discharged but re-presented with worsening shortness of breath; troponin was 13 ng/mL and BNP was 2261 pg/mL. She was taken for catheterization which demonstrated patent stents but severe cardiogenic shock with cardiac index of 1.2 L/min/m². Intra-aortic balloon pump was placed and inotropes started but support was inadequate and she was transitioned to peripheral VA-ECMO with Impella. Emergent endomyocardial biopsy was performed with histology unequivocally diagnostic of giant cell myocarditis (<i>Figure</i>). Immunosuppression with steroids, thymoglobulin, and tacrolimus was initiated. She had recurrent ventricular tachycardia requiring cardioversion but ultimately, underwent urgent transplant evaluation and was listed status 1 (PRA 72%, BMI 21, blood type B+). She was successfully transplanted but had primary graft dysfunction requiring further VA-ECMO support for 10 days. She recovered normal graft function and was discharged on postoperative day 35. <h3>Summary</h3> Giant cell myocarditis presents with variable clinical symptoms but is frequently characterized by acute heart failure, cardiogenic shock, heart block, and ventricular arrhythmias. Definitive diagnosis requires endomyocardial biopsy. Mechanical circulatory support and transplant can be used successfully in fulminant cases of giant cell myocarditis.

Extracorporeal Photopheresis With Low-Dose Immunosuppression in High-Risk Heart Transplant Patients-A Pilot Study.

In severely ill patients undergoing urgent heart transplant (HTX), immunosuppression carries high risks of infection, malignancy, and death. Low-dose immunosuppressive protocols have higher rejection rates. We combined extracorporeal photopheresis (ECP), an established therapy for acute rejection, with reduced-intensity immunosuppression. Twenty-eight high-risk patients (13 with high risk of infection due to infection at the time of transplant, 7 bridging to transplant via extracorporeal membrane oxygenation, 8 with high risk of malignancy) were treated, without induction therapy. Prophylactic ECP for 6 months (24 procedures) was initiated immediately postoperatively. Immunosuppression consisted of low-dose tacrolimus (8–10 ng/ml, months 1–6; 5–8 ng/ml, >6 months) with delayed start; mycophenolate mofetil (MMF); and low maintenance steroid with delayed start (POD 7) and tapering in the first year. One-year survival was 88.5%. Three patients died from infection (POD 12, 51, 351), and one from recurrence of cancer (POD 400). Incidence of severe infection was 17.9% (n = 5, respiratory tract). Within the first year, antibody-mediated rejection was detected in one patient (3.6%) and acute cellular rejection in four (14.3%). ECP with reduced-intensity immunosuppression is safe and effective in avoiding allograft rejection in HTX recipients with risk of severe infection or cancer recurrence.