Background: The incidence and clinical importance of vasoplegia after lung transplantation remains poorly studied. We describe the incidence of vasoplegia and its association with complications after lung transplantation.Methods: Perioperative data of 279 lung transplant recipients operated on from 2015 to 2020 in a UK hospital were analysed retrospectively.Results: Vasoplegia occurred in 41.6% of patients after lung transplantation (mild, 31.0%; moderate, 55.2%; severe, 13.8%). Compared with non-vasoplegic patients, vasoplegic patients had a higher incidence of any acute kidney injury, defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria (78.5% vs 65%, P=0.015), renal replacement therapy (47.4% vs 24.5%, P<0.001), and delayed chest closure (18.4% vs 9.2%, P=0.025); were ventilated longer (70 [32-368] vs 34 [19-105] h, P<0.001); and stayed longer in the ICU (12.9 [5-30] vs 6.8 [3-20] days, P<0.001). Mortality at 30 days and 1 yr was higher in patients with vasoplegia (11.2% vs 5.5% and 20.7% vs 11.7%, P=0.039, respectively). Severe vasoplegia represented a predictor of longer-term mortality (hazard ratio=1.65, P=0.008). Underlying infectious disease, increased BMI, higher preoperative pulmonary artery systolic pressure and bilirubin levels, lower glomerular filtration rate, and increased fresh frozen plasma transfusion were predictors of vasoplegia severity. Neutrophilia, leucocytosis, and increased C-reactive protein were associated with vasoplegia, but release of the neutrophil activation markers myeloperoxidase and heparin-binding protein was similar between groups.Conclusions: Influenced by preoperative status as well as procedural factors and inflammatory response, vasoplegia is a common and critical condition after lung transplantation with worse short-term outcomes and long-term survival.

Fungal infections are common and frequently associated with clinical failure in patients receiving extracorporeal membrane oxygenation (ECMO). Antifungal drugs have physicochemical characteristics associated with a higher likelihood of sequestration onto ECMO circuitry potentially leading to a subtherapeutic drug concentration. The percentage of sequestration of the antifungal drugs—caspofungin, posaconazole, and voriconazole—was determined using an ex vivo ECMO model. The circuits were primed with whole human blood, sodium chloride 0.9%, and human albumin solution. Serial 2 ml samples were taken at baseline, 0.5, 1, 2, 6, 12, and 24 hours after drug addition, paired with non-ECMO controls stored in a water bath at 37°C. Mean loss from the blood-primed ECMO circuits and controls at 24 hours relative to baseline were 80% and 61% for caspofungin ( p = ns), 64% and 11% for posaconazole ( p < 0.005), and 27% and 19% for voriconazole ( p < 0.05). Calculated AUC 0–24 showed a 44% for caspofungin ( p = ns), 30.6% posaconazole ( p < 0.005), and 9% loss for voriconazole ( p = 0.003) compared with the controls, suggesting therapeutic concentrations of these antifungal agents cannot be guaranteed with standard dosing in patients on ECMO. Posaconazole exhibited the greatest loss to the ECMO circuit correlating with both high lipophilicity and protein binding of the drug.

Patients suffering from end-stage heart failure tend to have high mortality rates. With growing numbers of patients progressing into severe heart failure, the shortage of available donors is a growing concern, with less than 10% of patients undergoing cardiac transplantation (CTx). Fortunately, the use of left ventricular assist devices (LVADs), a variant of mechanical circulatory support has been on the rise in recent years. The expansion of LVADs has led them to be incorporated into a variety of clinical settings, based on the goals of therapy for patients ailing from heart failure. However, with an increase in the use of LVADs, there are a host of complications that arise with it. One such complication is the development and progression of aortic regurgitation (AR) which is noted to adversely influence patient outcomes and compromise pump benefits leading to increased morbidity and mortality. The underlying mechanisms are likely multifactorial and involve the aortic root-aortic valve (AV) complex, as well as the LVAD device, patient, and other factors, all of them alter the physiological mechanics of the heart resulting in AV dysfunction. Thus, it is imperative to screen patients before LVAD implantation for AR, as moderate or greater AR requires a concurrent intervention at the time of LVADs implantation. No current strict guidelines were identified in the literature search on how to actively manage and limit the development and/or progression of AR, due to the limited information. However, some recommendations include medical management by targeting fluid overload and arterial blood pressure, along with adjusting the settings of the LVADs device itself. Surgical interventions are to be considered depending on patient factors, goals of care, and the underlying pathology. These interventions include the closure of the AV, replacement of the valve, and percutaneous approach via percutaneous occluding device or transcatheter aortic valve implantation. In the present review, we describe the interaction between AV and LVAD placement, in terms of patient management and prognosis. Also it is provided a comprehensive echocardiographic strategy for the precise assessment of AV regurgitation severity.

Heart transplantation is the reference standard treatment for advanced acute and chronic heart failure, although limited by the scarcity of donor hearts. Careful selection of transplant candidates is therefore essential in combination with optimal donor recipient matching. In the current era, most surgeons use the bicaval heart transplant technique. Approximately half of the patients receiving a heart transplant are on mechanical circulatory support. Allograft rejection is clinically categorized according to its temporal occurrence (hyper-acute, acute, and chronic) and by the underlying mechanism (cellular, antibody-mediated, and mixed). The calcineurin inhibitors ciclosporin and tacrolimus are the cornerstones of current maintenance immunosuppression regimens and are used in combination with an anti-proliferative agent and corticosteroids to prevent rejection. The target of rapamycin inhibitors offer an alternative to chronic anti-rejection treatment. Despite the increasing complexity of heart transplant recipients, survival is improving progressively.

Heart transplantation is the reference standard treatment for advanced acute and chronic heart failure, although limited by the scarcity of donor hearts. Careful selection of transplant candidates is therefore essential in combination with optimal donor recipient matching. In the current era, most surgeons use the bicaval heart transplant technique. Approximately half of the patients receiving a heart transplant are on mechanical circulatory support. Allograft rejection is clinically categorized according to its temporal occurrence (hyper-acute, acute, and chronic) and by the underlying mechanism (cellular, antibody-mediated, and mixed). The calcineurin inhibitors ciclosporin and tacrolimus are the cornerstones of current maintenance immunosuppression regimens and are used in combination with an anti-proliferative agent and corticosteroids to prevent rejection. The target of rapamycin inhibitors offer an alternative to chronic anti-rejection treatment. Despite the increasing complexity of heart transplant recipients, survival is improving progressively.

Abstract Aims Altered mechanical load in response to injury is a main driver of myocardial interstitial fibrosis. No current in vitro model can precisely modulate mechanical load in a multicellular environment while maintaining physiological behaviour. Living myocardial slices (LMS) are a 300 μm‐thick cardiac preparation with preserved physiological structure and function. Here we apply varying degrees of mechanical preload to rat and human LMS to evaluate early cellular, molecular, and functionality changes related to myocardial fibrosis. Methods and results Left ventricular LMS were obtained from Sprague Dawley rat hearts and human cardiac samples from healthy and failing (dilated cardiomyopathy) hearts. LMS were mounted on custom stretchers and two degrees of diastolic load were applied: physiological sarcomere length (SL) (SL = 2.2 μm) and overload (SL = 2.4 μm). LMS were maintained for 48 h under electrical stimulation in circulating, oxygenated media at 37°C. In overloaded conditions, LMS displayed an increase in nucleus translocation of Yes‐associated protein (YAP) and an up‐regulation of mechanotransduction markers without loss in cell viability. Expression of fibrotic and inflammatory markers, as well as Collagen I deposition were also observed. Functionally, overloaded LMS displayed lower contractility (7.48 ± 3.07 mN mm−2 at 2.2 SL vs. 3.53 ± 1.80 mN mm−2 at 2.4 SL). The addition of the profibrotic protein interleukin‐11 (IL‐11) showed similar results to the application of overload with enhanced fibrosis (8% more of collagen surface coverage) and reduced LMS contractility at physiological load. Conversely, treatment with the Transforming growth factor β receptor (TGF‐βR) blocker SB‐431542, showed down‐regulation of genes associated with mechanical stress, prevention of fibrotic response and improvement in cardiac function despite overload (from 2.40 ± 0.8 mN mm−2 to 4.60 ± 1.08 mN mm−2). Conclusions The LMS have a consistent fibrotic remodelling response to pathological load, which can be modulated by a TGF‐βR blocker. The LMS platform allows the study of mechanosensitive molecular mechanisms of myocardial fibrosis and can lead to the development of novel therapeutic strategies.

Primary graft dysfunction (PGD) is a major determinant of morbidity and mortality following lung transplantation. Delineating basic mechanisms and molecular signatures of PGD remain a fundamental challenge. This pilot study examines if the pulmonary volatile organic compound (VOC) spectrum relate to PGD and postoperative outcomes. The VOC profiles of 58 bronchoalveolar lavage fluid (BALF) and blind bronchial aspirate samples from 35 transplant patients were extracted using solid-phase-microextraction and analyzed with comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry. The support vector machine algorithm was used to identify VOCs that could differentiate patients with severe from lower grade PGD. Using 20 statistically significant VOCs from the sample headspace collected immediately after transplantation (< 6 h), severe PGD was differentiable from low PGD with an AUROC of 0.90 and an accuracy of 0.83 on test set samples. The model was somewhat effective for later time points with an AUROC of 0.80. Three major chemical classes in the model were dominated by alkylated hydrocarbons, linear hydrocarbons, and aldehydes in severe PGD samples. These VOCs may have important clinical and mechanistic implications, therefore large-scale study and potential translation to breath analysis is recommended.

Although the activated partial thromboplastin time (aPTT) has historically been the method of choice for anticoagulation monitoring in patients undergoing mechanical circulatory support with intravenous unfractionated heparin, it is being progressively superseded by the anti-factor Xa (anti-Xa) method. A retrospective single-arm, single-centre analysis of 20 patients who underwent total artificial heart implantation entailed simultaneous determinations of aPTT and anti-Xa. Agreement between these parameters was assessed using the Bland-Altman method. Despite a positive correlation between aPTT and anti-Xa, normal target ranges were poorly aligned: from 5th to 30th postoperative day, for anti-Xa values of 0.2 and 0.4 U/ml corresponding aPTT values were 52.1 and 65.2 s, 7.9 and 14.8 lower than predicted values, respectively. This was not associated with thromboembolic sequalae. It was not possible to demonstrate a significant relationship between the predictor variables (postoperative day; white blood cell count; C-reactive protein concentration; alanine transaminase and alkaline phosphatase level; bilirubin; haemoglobin; albumin and total protein concentration) and the agreement between aPTT and anti-Xa levels. In summary, when anti-Xa levels were used to guide anticoagulation therapy, corresponding aPTT levels were low with respect to target range. Methodology applied in this study is generalizable to other forms of mechanical circulatory support.

Aim: Hyperlactatemia is common post-heart transplantation. Lactate measurements in the first 24 h were analyzed with respect to mortality. Methods: A total of 153 consecutive cardiac transplant patients were reviewed. Recipients of organs maintained in a state of ex vivo perfusion were included. Results: A total of 143 heart recipients were included. Hyperlactatemia (>2 mmol/l) was present in all patients. Despite maximum lactate and lactate clearance being significantly higher in nonsurvivors (p = 0.002, p = 0.004), neither receiver operator curve analysis nor multivariate logistic regression showed association with 1-year mortality. In comparison, the minimum lactate was significantly associated with mortality (area under the curve 0.728 [p < 0.001]; odds ratio 1.28 [95% 1.01-162; p = 0.04]). Conclusion: The minimum lactate, a surrogate of persistent hyperlactatemia, was demonstrated to be superior compared with maximum lactate and lactate clearance in determining patient prognosis.

Mechanical circulatory support forms a crucial and expanding element of advanced heart failure management. Short-term assistance is delivered in emergency situations or where the underlying condition is likely to quickly worsen, and these approaches are discussed in Chapter 30. This chapter focuses on implantable devices intended for the medium and long term. The first half of the chapter is aimed directly at practical clinical management, whilst the second half considers the evidence base for contemporary practice. The chapter concludes by considering new paradigms for implantable cardiac support. Most frequently, these devices support left ventricular function (left ventricular assist devices), and this comprises the majority of our discussion.

Ex vivo lung perfusion is an indispensable tool in the armamentarium of any lung transplant center. It helps to increase an already shrinking donor pool by offering a chance to assess suboptimal donor lungs in a systematic manner and improve them by treating them with low-molecular-weight perfusate. We offer a stepwise guide to carry out ex vivo lung perfusion on the donor lungs and criteria to accept them for transplants.

OBJECTIVESLeft ventricular assist device (LVAD) implantation for end-stage heart failure patients has been on the rise, providing a reliable long-term option. For some LVAD patients, longer term LV unloading leads to recovery; hence, the need for evaluating potential myocardial recovery and weaning eligibility has emerged.METHODSAll patients who underwent contemporary LVAD explantation at our institution between 2009 and 2020 were included in the study. Patients in New York Heart Association I, left ventricular ejection fraction >40%, a cardiac index >2.4 l/min and a peak oxygen intake >50% predicted underwent a 4-phase weaning assessment. A minimally invasive approach using a titanium plug was the surgery of choice in the most recent explants. Kaplan-Meier curves were used to estimate the survival at 1 and 5 years.RESULTSTwenty-six patients (17 HeartMate II, 9 HeartWare) underwent LVAD explantation after a median 317 days of support [IQ (212-518)], range 131-1437. Mean age at explant was 35.8 ± 12.7 years and 85% were males. Idiopathic dilated cardiomyopathy was the underlying diagnosis in 70% of cases. Thirteen (48%) patients were on short-term mechanical circulatory support and 60% required intensive care unit admission prior to the LVAD implantation. At 1 year, Kaplan-Meier estimated survival was 88%, whereas at 6 years, it was 77%. The average left ventricular ejection fraction at 1 year post-explant was 44.25% ± 8.44.CONCLUSIONSThe use of a standardized weaning protocol (echocardiographic and invasive) and a minimally invasive LVAD explant technique minimizes periprocedural complications and leads to good long-term device-free survival rates.

Reopening the chest in patients with left ventricular assist devices at the time of a heart transplant is challenging due to adhesions and the possibility of injury to vital structures. The sternal sparing bilateral thoracotomy approach utilized to implant a left ventricular assist device minimizes the chances of such injuries and offers a cosmetically better outcome. We demonstrate a procedure for implanting a left ventricular assist device in a 54-year-old man diagnosed with dilated cardiomyopathy who suffered rapid decompensation despite maximum medical therapy.

Abstract Donation after circulatory death lung transplantation is a well-established treatment for patients with end-stage lung disease. Ongoing developments in retrieval as well as ex vivo preservation techniques following deceased circulatory death donation, will help to reduce donor organ shortage and mortality on waiting list. We describe step by step different retrieval techniques for deceased circulatory death donors, our protocol for ex vivo lung preservation, as well as the minimally invasive off pump surgical approach as performed at Harefield Hospital NHS Trust for Lung Transplantation. Early and long-term outcomes with this technique, are comparable to those undergoing Lung Transplantation from Brain dead donors as per the international registry data.

Background. The increasing prevalence of heart failure has led to the expanded use of left ventricle assist devices (VADs) for end-stage heart failure patients worldwide. Technological improvements witnessed the development of miniaturized VADs and their implantation through less traumatic non-full sternotomy approaches using a lateral thoracotomy (LT). Although adoption of the LT approach is steadily growing, a lack of consensus remains regarding patient selection, details of the surgical technique, and perioperative management. Furthermore, the current literature does not offer prospective randomized studies or evidence-based guidelines for LT-VAD implantation. Methods. A worldwide group of LT-VAD experts was convened to discuss these key topics openly. After a PubMed search and review with all authors, a consensus was reached and an expert consensus paper on LT-VAD implantation was developed. Results. This document aims to guide clinicians in the selection of patients suitable for LT approaches and preoperative optimization. Details of operative techniques are described, with an overview of hemisternotomy and bilateral thoracotomy approaches. A review of the best surgical practices for placement of the pump, inflow cannula, and outflow graft provides advice on the best surgical strategies to avoid device malpositioning while optimizing VAD function. Experts' opinions on cardiopulmonary bypass, postoperative management, and approaches for pump exchange and explant are presented. This review also emphasizes the critical need for multidisciplinary teams and specific training. Conclusions. This expert consensus review provides a compact guide to LT for VAD implantation, from patient selection through intraoperative tips and postoperative management. (C) 2021 by The Society of Thoracic Surgeons

Background. We investigated changes in estimated glomerular filtration rate (eGFR) after left ventricular assist device (LVAD) implant and the impact on long-term outcomes. Methods. A retrospective analysis was conducted for 255 patients with LVADs, divided into 2 groups based on preimplant eGFR (<60 or >60 mL/min/1.73 m(2)) and into 6 grades (grade 1, >90 mL/min/1.73 m(2) normal; grade 2, 60-89 mild dysfunction; grade 3, 45-59 moderate; grade 4, 30-44 moderate to severe; grade 5, 15-29 severe; or grade 6, <15 kidney failure). Changes in eGFR and the impact on long-term outcome and survival were analyzed. Results. One-month postimplant eGFR of the total cohort increased from a baseline of 75.19 +/- 34.35 to 118.97 +/- 67.62 mL/min/1.73 m(2) (P < .001). eGRF 4 years postimplant was higher than baseline but not significantly (P = .48). Patients with a preimplant eGFR > 60 followed the same pattern as the entire cohort. The preimplant eGFR < 60 group had a significant increase at 1 month (P < .001), eGFR remained significantly higher than baseline 4 years postimplant (P = .032), and there was a sustained transition to improved distribution of renal function grade after LVAD implant. Post-LVAD implant survival at 1, 3, and 5 years for baseline eGFR > 60 was 76%, 54%, and 48% and for eGFR < 60 was 71%, 60%, and 48%, respectively (P = .92). Conclusions. Patients with a low preimplant eGFR derive benefit from LVAD therapy, with eGFR remaining elevated above preimplant levels. Preimplant renal dysfunction did not impact negatively on long-term morbidity and mortality. (C) 2021 by The Society of Thoracic Surgeons

For patients with end-stage lung disease, LTx remains the only therapeutic option toward better chance of survival as well as improved quality of life. According to the International Society for Heart and Lung Transplantation (ISHLT) Transplant Registry, the number of LTx procedures has been rising despite limitations in available and suitable donor lungs and in the face of persistent donor shortages.1 The modern era of LTx is characterized by increasing complexity of recipient candidates including those receiving bridging extracorporeal support, a trend toward acceptance of suboptimal or extended criteria donors, and increasingly complicated surgical strategies.

INTRODUCTION:We describe a patient who developed severe aortic regurgitation following Impella left ventricular assist device implantation requiring aortic valve replacement.CASE REPORT:A previously healthy 34-year-old female presented with chest pain and flu-like symptoms. Electrocardiogram showed widespread ST elevation and serum troponin was raised, consistent with myocarditis. Coronary angiography was normal but the right coronary artery dissected. Subsequent cardiogenic shock required veno-arterial extracorporeal membrane oxygenation and Impella implantation. Myocardial function recovered, but upon removal of the Impella, severe aortic regurgitation was present and she underwent aortic valve replacement, making a full recovery.DISCUSSION:Aortic regurgitation is a rare complication of Impella implantation, and to our knowledge, this is the first reported case successfully treated with aortic valve replacement. Veno-arterial extracorporeal membrane oxygenation and Impella used in tandem are relatively novel, and may add synergistic benefit to strategies for acute cardiogenic shock.CONCLUSION:Echocardiography must include frequent assessment of both valvular and myocardial function after Impella removal.

Cystic fibrosis (CF) is one of the most common indications for lung transplant (LTx) and nearly one-third of the LTx worldwide are performed in people with CF (PwCF). Due to vast developments in diagnostic modalities, antibiotic therapies, and management of associated comorbidities in dedicated and experienced centres, over the past few decades, more PwCF are reaching adulthood than ever before. This has increased the burden on transplant programs particularly in a universal donor shortage scenario. To improve the donor pool a diligent and proactive donor care management, acceptance of marginal organs and utilisation of ex-vivo lung perfusion systems for organ preservation, assessment, and improvement is being advocated widely. LTx is not a readily available therapy and the average waiting time is 18 months in the UK. Therefore, it is essential that PwCF are referred for LTx assessment when their disease is stable, before respiratory deterioration leads to overall deconditioning of the patients. Once listed for LTx, it is crucial to control waiting list mortality by prioritising rapidly deteriorating patients through schemes like the lung allocation score, national urgent and super-urgent waiting lists, and institutional highlighting of deteriorating patients that do not meet other urgent criteria. LTx in PwCF is challenging due to colonisation of the respiratory tract with multi-drug resistant organisms, associated comorbidities such as diabetes, liver disease, gastro-oesophageal reflux, and distal intestinal obstruction syndrome (DIOS) and CF-specific technical difficulties (adhesions due to prior pneumothoraces or pleurodesis, or bronchial collaterals that increase surgical time). Hilar lymphadenopathy and bronchial collaterals may increase surgical time, organ ischemia time, intra and post-operative bleeding, and blood transfusions. Advances in immunosuppression, prophylactic anti-viral and anti-fungal therapies, early ambulation and rigorous physiotherapy, and meticulous postoperative follow up with spirometry, x-rays, and bronchoscopies to detect rejection at the early stage followed by its efficient treatment have helped to improve post-LTx survival in the CF patients. Constant development in the surgical field with adoption of off-pump transplantation, sternal sparing bilateral thoracotomy approach, and utilisation of mechanical circulatory assist as a bridge to transplant and as a support for primary graft failure strives for better outcomes. However, chronic lung allograft dysfunction, chronic refractory infections, malignancies, and CF associated comorbidities remain major determinants of post-LTx long term survival. Despite this, CF patients are often good candidates for re-do LTx with improving survival outcomes. In this chapter, we are compiling the different aspects of LTx in PwCF emphasising the advances in bridge to transplantation, the surgical approach, management of primary graft failure, and immunosuppression as well as complications post-transplant.