Outcomes of heart transplant recipients bridged with percutaneous versus durable left ventricular assist devices.

BACKGROUND: The new United Network for Organ Sharing (UNOS) heart allocation policy prioritizes temporary percutaneous over durable left ventricular assist devices (LVAD) as bridge to transplant. We sought to examine 1-year outcomes of heart transplant recipients bridged with Impella versus durable LVADs. METHODS: All primary adult orthotopic heart transplant recipients registered in UNOS between January 2016 and June 2021 were analyzed. Recipients were identified as being bridged with isolated durable or percutaneous LVAD at the time of transplant. Baseline characteristics were compared and 1-year survival was examined using the Kaplan Meier method and multivariable Cox proportional hazards regression. RESULTS: During our study period, heart transplant recipients bridged with LVADs were divided between 5422(94%) durable and 324(6%) percutaneous options. Impella-bridged recipients were more likely to be status 1A under the old allocation system (98% vs. 70%, p < .01) and status 2 or higher under the new allocation system (99% vs. 24%, p < .01). Impella-bridged recipients were less likely to be obese (27% vs. 42%, p < .01), have ischemic cardiomyopathy (27% vs. 34%, p < .01), and were more likely to be on inotropic agents at the time of transplant (68% vs. 6%, p < .01). One-year post-transplant survival was not significantly different between the two groups on univariable (HR .87, 95% CI .56-1.37) or multivariable analysis (aHR .63, 95% CI .37-1.07). CONCLUSIONS: Following the UNOS allocation policy change, Impella utilization has increased with no significant difference in 1-year survival compared to bridge with durable LVADs. Impella may be a reasonable alternative to durable LVADs in select patients.

The allograft injury marker CXCL9 determines prognosis of anti-HLA antibodies after lung transplantation.

Despite the common detection of non-donor specific anti-HLA antibodies (non-DSAs) after lung transplantation, their clinical significance remains unclear. In this retrospective single-center cohort study of 325 lung transplant recipients, we evaluated the association between donor-specific HLA antibodies (DSAs) and non-DSAs with subsequent CLAD development. DSAs were detected in 30% of recipients and were associated with increased CLAD risk, with higher HRs for both de novo and high MFI (>5000) DSAs. Non-DSAs were detected in 56% of recipients, and 85% of DSA positive tests had concurrent non-DSAs. In general, non-DSAs did not increase CLAD risk in multivariable models accounting for DSAs. However, non-DSAs in conjunction with high BAL CXCL9 levels were associated with increased CLAD risk. Multivariable proportional hazards models demonstrate the importance of the HLA antibody-CXCL9 interaction: CLAD risk increases when HLA antibodies (both DSAs and non-DSAs) are detected in conjunction with high CXCL9. Conversely, CLAD risk is not increased when HLA antibodies are detected with low CXCL9. This study supports the potential utility of BAL CXCL9 measurement as a biomarker to risk stratify HLA antibodies for future CLAD. The ability to discriminate between high versus low-risk HLA antibodies may improve management by allowing for guided treatment decisions.

Benefits of both physical assessment and electronic health record review to assess frailty prior to heart transplant.

INTRODUCTION: Frailty status affects outcomes after heart transplantation, but the optimal way to assess frailty prior to transplant remains unknown. METHODS: This single-center, observational study assessed 44 heart transplant candidates for frailty using three methods. The Short Physical Performance Battery (SPPB) and Fried Frailty Phenotype (FFP) were used as two physical assessments of frailty. The Frailty Risk Score (FRS) was used as a chart-review based assessment measuring 20 different biopsychosocial and functional components, including biomarkers, depression, cognitive impairment, and sleep. RESULTS: We determined the correlation between FRS, SPPB, and FFP and how each correlated with clinical outcomes. Of 44 participants, mean age was 60 years. FRS correlated with SPPB and FFP (P = .043, P < .001, respectively). Higher frailty as measured by SPPB and FRS was significantly associated with lack of achieving waitlist status (P = .022; P = .002) and not being transplanted (P = .026; P = .008). Higher frailty by SPPB and FFP was also associated with mortality (P = .010; P = .025). CONCLUSION: SPPB and chart-review FRS showed potential for predicting waitlist and transplant status of heart transplant candidates, while SPPB and FFP were associated with mortality. Additional studies may serve to validate these observations.

Left main coronary artery compression in pulmonary hypertension.

Extrinsic compression of the left main coronary artery (LMCA) by a dilated pulmonary artery (PA) in the setting of pulmonary arterial hypertension (PAH) is an increasingly recognized disease entity. LMCA compression has been associated with angina, arrhythmia, heart failure, and sudden cardiac death in patients with PAH. Recent studies suggest that at least 6% of patients with PAH have significant LMCA compression. Screening for LMCA compression can be achieved with computed coronary tomography angiography, with a particular emphasis on assessment of PA size and any associated downward displacement and reduced takeoff angle of the LMCA. Indeed, evidence of a dilated PA (>40 mm), a reduced LMCA takeoff angle (<60°), and/or LMCA stenosis on CCTA imaging should prompt further diagnostic evaluation. Coronary angiography in conjunction with intravascular imaging has proven effective in diagnosing LMCA compression and guiding subsequent treatment. While optimal medical therapy and surgical correction remain in the clinician's arsenal, percutaneous coronary intervention has emerged as an effective treatment for LMCA compression. Given the prevalence of LMCA compression, its associated morbidity, and mortality, and the wide array of successful treatment strategies, maintaining a high degree of suspicion for this condition, and understanding the potential treatment strategies is critical.

Mitochondrial DNA Stimulates TLR9-Dependent Neutrophil Extracellular Trap Formation in Primary Graft Dysfunction.

The immune system is designed to robustly respond to pathogenic stimuli but to be tolerant to endogenous ligands to not trigger autoimmunity. Here, we studied an endogenous damage-associated molecular pattern, mitochondrial DNA (mtDNA), during primary graft dysfunction (PGD) after lung transplantation. We hypothesized that cell-free mtDNA released during lung ischemia-reperfusion triggers neutrophil extracellular trap (NET) formation via TLR9 signaling. We found that mtDNA increases in the BAL fluid of experimental PGD (prolonged cold ischemia followed by orthotopic lung transplantation) and not in control transplants with minimal warm ischemia. The adoptive transfer of mtDNA into the minimal warm ischemia graft immediately before lung anastomosis induces NET formation and lung injury. TLR9 deficiency in neutrophils prevents mtDNA-induced NETs, and TLR9 deficiency in either the lung donor or recipient decreases NET formation and lung injury in the PGD model. Compared with human lung transplant recipients without PGD, severe PGD was associated with high levels of BAL mtDNA and NETs, with evidence of relative deficiency in DNaseI. We conclude that mtDNA released during lung ischemia-reperfusion triggers TLR9-dependent NET formation and drives lung injury. In PGD, DNaseI therapy has a potential dual benefit of neutralizing a major NET trigger (mtDNA) in addition to dismantling pathogenic NETs.

Discovery of non-HLA antibodies associated with cardiac allograft rejection and development and validation of a non-HLA antigen multiplex panel: From bench to bedside.

We analyzed humoral immune responses to nonhuman leukocyte antigen (HLA) after cardiac transplantation to identify antibodies associated with allograft rejection. Protein microarray identified 366 non-HLA antibodies (>1.5 fold, P < .5) from a discovery cohort of HLA antibody-negative, endothelial cell crossmatch-positive sera obtained from 12 cardiac allograft recipients at the time of biopsy-proven rejection. From these, 19 plasma membrane proteins and 10 autoantigens identified from gene ontology analysis were combined with 48 proteins identified through literature search to generate a multiplex bead array. Longitudinal sera from a multicenter cohort of adult cardiac allograft recipients (samples: n = 477 no rejection; n = 69 rejection) identified 18 non-HLA antibodies associated with rejection (P < .1) including 4 newly identified non-HLA antigenic targets (DEXI, EMCN, LPHN1, and SSB). CART analysis showed 5/18 non-HLA antibodies distinguished rejection vs nonrejection. Antibodies to 4/18 non-HLA antigens synergize with HLA donor-specific antibodies and significantly increase the odds of rejection (P < .1). The non-HLA panel was validated using an independent adult cardiac transplant cohort (n = 21 no rejection; n = 42 rejection, >1R) with an area under the curve of 0.87 (P < .05) with 92.86% sensitivity and 66.67% specificity. We conclude that multiplex bead array assessment of non-HLA antibodies identifies cardiac transplant recipients at risk of rejection.

Heart transplantation in the early phase of the COVID-19 pandemic: A single-center case series.

The infectious disease coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization in March 2020. The impact of COVID-19 on solid organ transplantations, including heart transplantation, is currently unclear. Many transplant programs have been forced to swiftly re-evaluate and adapt their practices, leading to a marked decrease in transplants performed. This trend has been due to various factors, including increased donor COVID-19 screening scrutiny and recipient waiting list management in anticipation of COVID-19 critical care surge capacity planning. In the face of these unknown variables, determining when and how to proceed with transplantation in our population of patients with end-stage cardiomyopathies is challenging. Here, we describe our center's experience with orthotopic heart transplantation (OHT) in one of the country's pandemic epicenters, where we performed eight OHTs in the first 2 months after community spread began in late February 2020.

Prospective, multicenter, randomized, controlled trial evaluating the performance of a novel combination powder vs hemostatic matrix in cardiothoracic operations.

AIM: This trial compared the hemostatic performance of a novel combination powder (CP) to a control hemostatic matrix (HM) in cardiothoracic operations. METHODS: Patients meeting eligibility criteria were enrolled after providing informed consent. Subjects were randomized intraoperatively to receive CP (HEMOBLAST Bellows; Biom'up, France) or HM (FLOSEAL Hemostatic Matrix; Baxter Healthcare Corporation, Hayward, CA). Bleeding was assessed using a clinically validated, quantitative bleeding severity scale. The primary endpoint was total time to hemostasis (TTTH), from the start of device preparation, as an indicator of when a surgeon asks for a surgical hemostat until hemostasis was achieved. TTTH at 3 minutes was utilized for the primary analysis, while TTTH at 5 minutes was considered as a secondary endpoint. RESULTS: A total of 105 subjects were enrolled across four institutions. The primary efficacy endpoint for the superiority of CP relative to HM for success at achieving hemostasis within 3 minutes was met, with 64.2% of the CP group achieving hemostasis compared with 9.6% of the HM group, a difference of 54.54% (37.4%-71.6%; P < .001 for superiority). The secondary efficacy endpoint was also met, with 92.5% of the CP group achieving hemostasis at 5 minutes versus 44.2% in the HM group, a difference of 48.2% (31.1%-65.4%; P < .001 for noninferiority). There were no device-related adverse events. CONCLUSIONS: In this multicenter, randomized, controlled trial, comparison of CP to HM revealed CP superiority and noninferiority for TTTH at 3 and 5 minutes, respectively.

Current status of normothermic ex-vivo perfusion of cardiac allografts.

PURPOSE OF REVIEW: Ex-vivo perfusion has emerged in recent years as an alternative to cold static preservation of organs harvested for transplant. Normothermic ex-vivo perfusion, the subject of this review, maintains the donor heart in a near physiologic state, and allows the transplant team to monitor and control perfusion to the organ prior to implantation. A growing body of evidence has established the safety and viability of this technique, which may improve on current standards of donor management. RECENT FINDINGS: Following initial single-arm studies over a decade ago, ex-vivo perfusion has been studied in a prospective, randomized fashion in standard donor hearts (PROCEED II trial). The short and intermediate-term results demonstrated similar outcomes compared with cold storage with significantly shorter cold ischemic time. Since then, ex-vivo perfusion has been studied in extended-criteria donor hearts, first in observational studies, and currently in randomized, prospective fashion in the recently completed EXPAND-Heart trial, which is anticipated to be reported in 2020. SUMMARY: Normothermic ex-vivo perfusion has an established literature base and holds promise for changing current practices of heart preservation. Results of forthcoming pivotal studies will help determine its role in more widespread clinical adoption.

Evaluation of the safety and efficacy of a new hemostatic powder using a quantitative surface bleeding severity scale.

AIMS OF THE STUDY: The safety and efficacy of a hemostatic powder (HP) versus a control agent, absorbable gelatin sponge and thrombin (G + T), were assessed, using a validated, quantitative bleeding severity scale. METHODS: Subjects were randomized to receive HP (256 subjects) or G + T (132 subjects) for treatment of minimal, mild, or moderate bleeding at 20 investigational sites. The primary efficacy endpoint was non-inferiority of HP relative to G + T for success at achieving hemostasis within 6 minutes. Secondary endpoints in rank order included: superiority of HP relative to G + T in mean preparation time; non-inferiority of HP relative to G + T for achieving hemostasis within 3 min; superiority of HP relative to G + T for achieving hemostasis within 6 min; and superiority of HP relative to G + T for success for achieving hemostasis within 3 min. RESULTS: A total of 388 subjects were included in the primary efficacy analysis. At 6 min, hemostasis was achieved in 93.0% (238/256) of the HP group compared to 77.3% (102/132) of the G + T group (non-inferiority P < 0.0001, superiority P < 0.0001). All secondary endpoints were met. Complications were comparable between treatment groups. CONCLUSIONS: HP had superior rates of hemostasis, shorter preparation time, and a similar safety profile compared to G + T in this prospective, randomized trial using quantitative bleeding severity criteria.

Lung transplantation in the Lung Allocation Score era: Medium-term analysis from a single center.

In 2005, the Lung Allocation Score (LAS) was implemented as the allocation system for lungs in the US. We sought to compare 5-year lung transplant outcomes before and after the institution of the LAS. Between 2000 and 2011, 501 adult patients were identified, with 132 from January 2000 to April 2005 (Pre-LAS era) and 369 from May 2005 to December 2011 (Post-LAS era). Kruskal-Wallis or chi-squared test was used to determine significance between groups. Survival was censored at 5 years. Overall, the post-LAS era was associated with more restrictive lung disease, higher LAS scores, shorter wait-list times, more preoperative immunosuppression, and more single lung transplantation. In addition, post-LAS patients had higher O2 requirements with greater preoperative pulmonary impairment. Postoperatively, 30-day mortality improved in post-LAS era (1.6% vs 5.3%, P = .048). During the pre- and post-LAS eras, 5-year survival was 52.3% and 55.3%, respectively (P = .414). The adjusted risk of mortality was not different in the post-LAS era (P = .139). Freedom from chronic lung allograft dysfunction was significantly higher in the post-LAS era (P = .002). In this single-center report, implementation of the LAS score has led to allocation to sicker patients without decrement in short- or medium-term outcomes. Freedom from CLAD at 5 years is improving after LAS implementation.

Heart and heart-liver transplantation in adults with failing Fontan physiology.

BACKGROUND: As the population of patients with a Fontan palliation grows so does, the number of patients with cardiac failure necessitating orthotopic heart transplant (OHT) and combined heart-liver transplant (CHLT). There is recent evidence that current era cardiac transplant in Fontan patients has improved outcomes, but most studies have a preponderance of pediatrics patients in their cohorts. We examine our institutional experience with adult OHT and CHLT transplantation for failed Fontan physiology. METHODS AND RESULTS: Retrospective analysis of patients at the Ahmanson/UCLA Adult Congenital Heart Disease Center who underwent OHT or CHLT for failing Fontan physiology from January 1, 2002 to May 31, 2017. We identified 20 patients with single-ventricle physiology and Fontan palliation who underwent OHT or CHLT. The median age was 29.5 years (range 19-44). Five patients underwent CHLT because of biopsy proven hepatic cirrhosis. The median length of hospital stay was 23 days (range 8-76) post-OHT and 51 days (range 26-77) post-CHLT. During a median follow-up of 56 months (range 2-178), there was one mortality occurring at 34 months post-OHT due to coronary vasculopathy. Most frequent early postoperative complications included bleeding and infection (55% and 20%, respectively) and surgical reintervention for bleeding complications (n = 8, 40%). One CHLT patient experienced clinically significant hepatic rejection requiring admission and steroid treatment. CONCLUSIONS: Despite inherent risks and complexities of OHT or CHLT in patients with a failed Fontan, transplant is a reasonable therapy. Peri- and postoperative complications are common and may require surgical reintervention. Continued observation of practices and unifying themes may help improve patient selection, pre- and postoperative treatment and ultimately outcomes.

Temporary Venoarterial Extracorporeal Membrane Oxygenation: Ten-Year Experience at a Cardiac Transplant Center.

OBJECTIVE: Advances in extracorporeal membrane oxygenation (ECMO) have enabled rapid deployment in a wide range of clinical settings. We report our experience with venoarterial (VA) ECMO in adult patients over 10 years and aim to identify predictors of mortality. DESIGN: This is a retrospective analysis of all adult patients undergoing VA ECMO at a tertiary care center from January 1, 2004, to December 31, 2013. RESULTS: A total of 224 consecutive cases were reviewed. Eighty (35.7%) patients survived to discharge and 144 (64.3%) patients died. Patients requiring ECMO for heart transplant graft failure had lower mortality (51.6%) compared to all other etiologies (69.1%; P = .02). Forty-two percent (94 of the 224) of the patients required cardiopulmonary resuscitation (CPR) preceding ECMO and had higher rate of in-hospital mortality (74.5%) compared with patients without cardiac arrest (56.9%; P = .01). Patients with less than 30 minutes of CPR had a mortality rate of 40.0% compared to 91.4% for CPR > 30 minutes ( P = .001). In all, 24.1% of patients (54 of the 224) experienced ECMO-associated complications without significant increase in mortality, and 22.3% (50 of the 224) of the patients were transitioned to ventricular assist devices (VADs) or transplant. Patients bridged to a VAD including left ventricular assist devices and biventricular assist devices had a mortality rate of 56.1% versus 22.2% when bridged directly to transplant ( P = .01). Paradoxically, patients with an ejection fraction (EF) > 35% had a higher mortality compared to patients with an EF < 35% (75.3% vs 49.4%, respectively, P = .001). CONCLUSION: Extracorporeal membrane oxygenation in patients with heart transplant graft failure had the best outcome. In patients who had cardiac arrest, prolonged CPR > 30 minutes was associated with very high mortality. Paradoxically, patients with EF > 35% had a higher mortality than patients with EF < 35%, likely reflecting patients with diastolic heart failure or noncardiac causes necessitating ECMO. For transplant candidates, direct bridge from ECMO to transplant could achieve a very good outcome.

Primary graft dysfunction in heart transplantation.

PURPOSE OF REVIEW: Primary graft dysfunction (PGD) is common early postheart transplantation; however, use of standardized definitions remains inconsistent. This review focuses on understanding the incidence, classification, risk factors, and management of PGD. RECENT FINDINGS: The incidence and mortality of PGD in heart transplant varies considerably in the published literature ranging from 1.0% to 31% and 3% to 75%, respectively. There is also considerable variation in management strategies with current data favoring early intervention. SUMMARY: PGD in heart transplantation remains a challenging problem associated with significant mortality and morbidity. There is need for a consistent and accessible definition to better define associated risk factors and optimize management strategies.

Voriconazole increases the risk for cutaneous squamous cell carcinoma after lung transplantation.

Lung transplant recipients (LTR) are at high risk of cutaneous squamous cell carcinoma (SCC). Voriconazole exposure after lung transplant has recently been reported as a risk factor for SCC. We sought to study the relationship between fungal prophylaxis with voriconazole and the risk of SCC in sequential cohorts from a single center. We evaluated 400 adult LTR at UCLA between 7/1/2005 and 12/22/2012. On 7/1/2009, our center instituted a protocol switch from targeted to universal antifungal prophylaxis for at least 6 months post-transplant. Using Cox proportional hazards models, time to SCC was compared between targeted (N = 199) and universal (N = 201) prophylaxis cohorts. Cox models were also used to assess SCC risk as a function of time-dependent cumulative exposure to voriconazole and other antifungal agents. The risk of SCC was greater in the universal prophylaxis cohort (HR 2.02, P < 0.01). Voriconazole exposure was greater in the universal prophylaxis cohort, and the cumulative exposure to voriconazole was associated with SCC (HR 1.75, P < 0.01), even after adjustment for other important SCC risk factors. Voriconazole did not increase the risk of advanced tumors. Exposure to other antifungal agents was not associated with SCC. Voriconazole should be used cautiously in this population.

Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial.

BACKGROUND: The Organ Care System is the only clinical platform for ex-vivo perfusion of human donor hearts. The system preserves the donor heart in a warm beating state during transport from the donor hospital to the recipient hospital. We aimed to assess the clinical outcomes of the Organ Care System compared with standard cold storage of human donor hearts for transplantation. METHODS: We did this prospective, open-label, multicentre, randomised non-inferiority trial at ten heart-transplant centres in the USA and Europe. Eligible heart-transplant candidates (aged >18 years) were randomly assigned (1:1) to receive donor hearts preserved with either the Organ Care System or standard cold storage. Participants, investigators, and medical staff were not masked to group assignment. The primary endpoint was 30 day patient and graft survival, with a 10% non-inferiority margin. We did analyses in the intention-to-treat, as-treated, and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT00855712. FINDINGS: Between June 29, 2010, and Sept 16, 2013, we randomly assigned 130 patients to the Organ Care System group (n=67) or the standard cold storage group (n=63). 30 day patient and graft survival rates were 94% (n=63) in the Organ Care System group and 97% (n=61) in the standard cold storage group (difference 2·8%, one-sided 95% upper confidence bound 8·8; p=0·45). Eight (13%) patients in the Organ Care System group and nine (14%) patients in the standard cold storage group had cardiac-related serious adverse events. INTERPRETATION: Heart transplantation using donor hearts adequately preserved with the Organ Care System or with standard cold storage yield similar short-term clinical outcomes. The metabolic assessment capability of the Organ Care System needs further study. FUNDING: TransMedics.

Altered Exosomal RNA Profiles in Bronchoalveolar Lavage from Lung Transplants with Acute Rejection.

RATIONALE: The mechanism by which acute allograft rejection leads to chronic rejection remains poorly understood despite its common occurrence. Exosomes, membrane vesicles released from cells within the lung allograft, contain a diverse array of biomolecules that closely reflect the biologic state of the cell and tissue from which they are released. Exosome transcriptomes may provide a better understanding of the rejection process. Furthermore, biomarkers originating from this transcriptome could provide timely and sensitive detection of acute cellular rejection (AR), reducing the incidence of severe AR and chronic lung allograft dysfunction and improving outcomes. OBJECTIVES: To provide an in-depth analysis of the bronchoalveolar lavage fluid exosomal shuttle RNA population after lung transplantation and evaluate for differential expression between acute AR and quiescence. METHODS: Serial bronchoalveolar lavage specimens were ultracentrifuged to obtain the exosomal pellet for RNA extraction, on which RNA-Seq was performed. MEASUREMENTS AND MAIN RESULTS: AR demonstrates an intense inflammatory environment, skewed toward both innate and adaptive immune responses. Novel, potential upstream regulators identified offer potential therapeutic targets. CONCLUSIONS: Our findings validate bronchoalveolar lavage fluid exosomal shuttle RNA as a source for understanding the pathophysiology of AR and for biomarker discovery in lung transplantation.

Neutrophil extracellular traps are pathogenic in primary graft dysfunction after lung transplantation.

RATIONALE: Primary graft dysfunction (PGD) causes early mortality after lung transplantation and may contribute to late graft failure. No effective treatments exist. The pathogenesis of PGD is unclear, although both neutrophils and activated platelets have been implicated. We hypothesized that neutrophil extracellular traps (NETs) contribute to lung injury in PGD in a platelet-dependent manner. OBJECTIVES: To study NETs in experimental models of PGD and in lung transplant patients. METHODS: Two experimental murine PGD models were studied: hilar clamp and orthotopic lung transplantation after prolonged cold ischemia (OLT-PCI). NETs were assessed by immunofluorescence microscopy and ELISA. Platelet activation was inhibited with aspirin, and NETs were disrupted with DNaseI. NETs were also measured in bronchoalveolar lavage fluid and plasma from lung transplant patients with and without PGD. MEASUREMENTS AND MAIN RESULTS: NETs were increased after either hilar clamp or OLT-PCI compared with surgical control subjects. Activation and intrapulmonary accumulation of platelets were increased in OLT-PCI, and platelet inhibition reduced NETs and lung injury, and improved oxygenation. Disruption of NETs by intrabronchial administration of DNaseI also reduced lung injury and improved oxygenation. In bronchoalveolar lavage fluid from human lung transplant recipients, NETs were more abundant in patients with PGD. CONCLUSIONS: NETs accumulate in the lung in both experimental and clinical PGD. In experimental PGD, NET formation is platelet-dependent, and disruption of NETs with DNaseI reduces lung injury. These data are the first description of a pathogenic role for NETs in solid organ transplantation and suggest that NETs are a promising therapeutic target in PGD.

Normothermic donor heart perfusion: current clinical experience and the future.

Following the first successful heart transplant in 1967, more than 100,000 heart transplants have been carried out worldwide. These procedures have mostly relied on cold ischaemic preservation of the donor heart because this simple technique is inexpensive and relatively reliable. However, the well-known limitations of cold ischaemic preservation imposes significant logistical challenges to heart transplantation which put a ceiling on the immediate success on this life-saving therapy, and limits the number of donor hearts that can be safely transplanted annually. Although the theoretical advantages of normothermic donor heart perfusion have been recognised for over a century, the technology to transport donor hearts in this state has only been developed within the last decade. The Organ Care System (OCS) which is designed and manufactured by TransMedics Inc. is currently the only commercially available device with this capability. This article reviews the history of normothermic heart perfusion and the clinical experience with the TransMedics OCS to date. We have also attempted to speculate on the future possibilities of this innovative and exciting technology.

Successful use of extracorporeal membrane oxygenation in an adult patient with toxic shock-induced heart failure.

Cardiomyopathy secondary to toxic shock syndrome (TSS) is an uncommon but potentially life-threatening problem. We report the case of a 51-year-old male who presented with profound cardiogenic shock and multiorgan failure that could not be managed by conventional therapy with intravenous fluids, vasopressors and inotropes. Venoarterial extracorporeal membrane oxygenation (VA ECMO) was instituted as a bridge to recovery. After administration of antibiotics and intravenous immunoglobulin, the patient's condition improved and he was successfully weaned off ECMO after 6 days. The patient recovered from multiorgan failure, and left ventricular ejection fraction improved from <10% pre-ECMO to 65% 8 months after discharge. This case supports the view that VA ECMO can be used successfully to support vital organ perfusion in patients with profound but reversible cardiomyopathy attributed to TSS.