Volatile organic compound profiling to explore primary graft dysfunction after lung transplantation.

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.

Anticoagulation in syncardia total artificial heart recipients: anti-factor Xa or activated partial thromboplastin time?

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patients undergoing mechanical circulatory support with intravenous unfractionated heparin, it is being progressively superseded by the anti-factor Xa (anti-Xa) method.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.

Sternal sparing bilateral symmetrical thoracotomy for implantation of left ventricular assist device.

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.

Ex vivo lung perfusion made easy.

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.

Impaired Baseline Renal Function May Not Influence Outcomes and Survival After Left Ventricular Assist Device Implantation.

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 m2) and into 6 grades (grade 1, >90 mL/min/1.73 m2 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 m2(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.

Expert Consensus Paper: Lateral Thoracotomy for Centrifugal Ventricular Assist Device Implant.

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.

A detailed explantation assessment protocol for patients with left ventricular assist devices with myocardial recovery.

OBJECTIVES: Left 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. METHODS: All 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. RESULTS: Twenty-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. CONCLUSIONS: The 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.

Cardiac tumors invading the right ventricle; Aggressive Surgical Management with backup mechanical circulatory support if necessary.

BACKGROUND: Primary cardiac tumors are exceedingly rare. Amongst the malignant types, sarcomas are the most frequently encountered. Treatment includes attempted aggressive surgical resection as the only curative option. We report our experience. METHODS: During the last five years, six patients presented at our institution with complex cardiac tumors with different underlying diagnoses and were at different stages of their disease. RESULTS: 6 patients with median age of 30-years-old underwent surgery in our centre. 3 patients had undergone debulking prior to surgery at our institution. In all patients, the tumor involved the right ventricle. One patient had biventricular involvement, the septum was involved in 4 patients, 2 patients had extracardiac growth, one invading both great vessels, one involving the pericardium and the hilar structures on the right side. Complete resection was achieved in 4 cases, 3 with successful resection-reconstruction, one with cardiectomy and implantation of a total artificial heart. 5 patients are currently alive, 4 free of recurrence. CONCLUSIONS: Complete radical surgery is the only curative treatment for patients suffering from cardiac tumors. The availability of mechanical circulatory support allows for a more radical surgical approach even including total cardiectomy, possibly resulting in a significant increase in R0 resections.

Surgical explant of a right ventricular assist device with sternum-sparing technique.

The use of long-term mechanical assist devices for isolated right ventricular failure is rare. Herein, we describe our protocol for successful recovery of the right ventricle and subsequent explantation of a right ventricular assist device using a sternum-sparing technique and insertion of a titanium plug to occlude the coring defect of the inflow cannula.

The role of extracorporeal life support in the management with severe idiopathic pulmonary artery hypertension undergoing lung transplantation: are those patients referred too late?

BACKGROUND: Idiopathic pulmonary artery hypertension (iPAH) is a relatively minor indication for lung transplantation (LTx) with comparatively poorer outcomes. Extracorporeal life support (ECLS) in various forms is increasingly being used in the management of this entity. However, the data and experience with this therapy remains limited. We evaluated the role of ECLS in the management of severe iPAH patients as a bridge to LTx as well as post LTx support. METHODS: A retrospective analysis of iPAH patients that received LTx between January 2007 and May 2014 was performed. Early- and mid-term outcomes were analyzed for this patient cohort. Also, early and mid-term outcomes after LTx were compared to the control group of patients with other diagnoses using unadjusted analysis and 1:3 propensity score matching. RESULTS: Of 321 LTx performed during the study period in our centre 15 patients had iPAH as a cause of end-stage lung disease. Four iPAH (27%) patients were bridged to LTx utilizing ECLS in the form of veno-arterial ECMO and extra-corporeal CO2 removal device, whereas 9 patients (60%) required ECLS support for primary graft dysfunction (PGD) after surgery. Patients with iPAH required more frequently on-pump LTx, both pre and post LTx ECLS, and had significantly lower pO2/FiO2 ratio at 24, 48 and 72 hours after LTx. Also iPAH patients had significantly longer ICU and hospital stay. Whereas the incidence of postoperative bronchiolitis obliterans syndrome (BOS) and rejection was comparable to the control group, overall cumulative survival with up to 6 years follow-up was significantly poorer in the iPAH group. After propensity score matching, the results in terms of postoperative outcomes remained as in the unadjusted analysis. CONCLUSIONS: ECLS is an essential tool in the armamentarium of any lung transplant program treating iPAH with a potential of bridge patients to transplantation and to overcome graft dysfunction after LTx. Despite utilization of ECLS in the management of iPAH, the outcomes in terms of primary graft failure and survival remain poor compared to patients with other diagnoses.

Total artificial heart implantation after right ventricular intimal spindle cell sarcoma.

This paper describes the case of a patient with a high-grade spindle sarcoma in the right ventricle. The patient underwent total cardiectomy followed by the implantation of a total artificial heart. The patient had an uneventful postoperative course and remained tumour-free for 12 months; after that time period she underwent a heart transplant.

Direct Procurement of Donor Heart With Normothermic Regional Perfusion of Abdominal Organs.

PURPOSE: We wanted to evaluate if direct procurement of the heart is possible in combination with normothermic regional perfusion of abdominal organs in donors after circulatory death. DESCRIPTION: A donation after circulatory death pathway was used for a 41-year-old woman after an irreversible brain injury. After meeting criteria for the organ donation, the heart was retrieved and re-animated on ex situ perfusion system, and abdominal organs were perfused with normothermic regional perfusion. EVALUATION: All the donated organs and their recipients had excellent short-term outcome. CONCLUSIONS: We demonstrated a successful combination of direct procurement of the heart and normothermic regional perfusion of the abdominal organs.

It keeps on turning: Effects of prolonged long-term left ventricular assist device support as a bridge to heart transplantation.

OBJECTIVES:: Increasing incidence of end-stage heart failure has moved the therapy with left ventricular assist devices to the forefront of surgical treatment. Moreover, continuous sophistication in this technology has resulted in increasing proportion of patients on prolonged support. Early and late complications after left ventricular assist device as a bridge to transplantation and present factors associated with long-term support and long-term outcomes of patients supported for at least 1 year were compared. METHODS:: A total of 163 consecutive patients who underwent left ventricular assist device implantation as bridge to transplantation were included. A total of 79 patients were supported for at least 1 year (long-term support), whereas 84 patients were supported for less than 1 year (short-term group). RESULTS:: Factors associated with a successful long-term support were male gender (p < 0.001), cessation of smoking at least 6 months prior to surgery (p = 0.045), previous implantation of implantable cardioverter defibrillator (p = 0.001) and rapid postoperative extubation (p = 0.018). Regarding echocardiographic parameters, higher left ventricular mass (p = 0.013) and larger left ventricular-end systolic (p = 0.008) and diastolic (p = 0.005) diameters prior to left ventricular assist device implantation were associated with long-term support. Short-term group showed higher mortality and higher proportion of patients who underwent device exchange due to device failure, and left ventricular assist device explantation for myocardial recovery was less frequent in the long-term support (p < 0.001). In addition, patients from the long-term support had significantly higher incidence of higher-grade aortic regurgitation (p = 0.005). CONCLUSION:: Prolonged left ventricular assist device support as bridge to transplantation is associated with lower mortality and lower incidence of device failure requiring device exchange. However, long-term support reduces the chance of device explantation for myocardial recovery and increases the incidence of higher-grade aortic regurgitation in the follow-up.

Hybrid treatment of aortic valve regurgitation and right heart failure 22 years after heterotopic heart transplantation.

Clinical application of heterotopic heart transplantation is no longer pursued. However, a significant number of patients present again with deteriorating function of the native or recipient's heart. We describe the management of severe native aortic regurgitation and right heart failure in a patient following heterotopic heart transplantation. We performed a percutaneous closure of the insufficient native aortic valve followed by a surgical transposition of the donor's pulmonary artery from the recipient's right atrium to the pulmonary artery.

Mitral Valve Compression Induced Hypoxemia After Left Ventricular Assist Device Surgery: A Case Report.

Blood flow obstruction of left ventricular assist device (LVAD) is not uncommon. Causes of flow obstructions could be prepump, intrapump, and postpump. Clinical and echocardiographic parameters of LVAD obstruction vary substantially, ranging from being completely asymptomatic with unchanged functional status, normal filling pressures to frank cardiogenic shock. In the current case report, we present hypoxemia as an early presentation of LVAD inflow obstruction in the early postimplantation period in the absence of respiratory cause for hypoxemia.

Minimally Invasive Left Ventricular Assist Device Implantation: A Comparative Study.

Left ventricular assist device (LVAD) is now a routine therapy for advanced heart failure. Minimally invasive approach via thoracotomy for LVAD implantation is getting popular due to its potential advantage over the conventional sternotomy approach in terms of reduced risk at re-operation due to sternal sparing. We compared the approaches (thoracotomy and sternotomy) to determine the superiority. Minimally invasive approach involved fitting of the LVAD inflow cannula into left ventricle apex via left anterior thoracotomy and anastomosis of outflow graft to ascending aorta via right anterior thoracotomy. In the sternotomy approach, both the procedures were performed via sternotomy. Outcomes in patients after LVAD implantation were compared depending on these approaches for the surgery. Two hundred and five continuous flow LVAD implantations performed between July 2006 and June 2015 at a single center were divided based on surgical approach, that is, sternotomy (n = 180) and thoracotomy (n = 25) groups. There was no significant difference between the groups in relation to patient demographics, preoperative hemodynamic parameters, laboratory markers, or risk factors. There was no significant difference between the groups in terms of postoperative hemodynamic parameters, laboratory markers, bleeding and requirement of blood products, intensive care unit, and hospital stay or complications of LVAD surgery. There were no significant differences in terms of long-term survival (Log-Rank P = 0.953), however, thoracotomy, compared to sternotomy approach, incurred significantly less requirement of temporary right ventricular assist (4 vs. 19.4%, P = 0.041). Minimally invasive bilateral thoracotomy approach for LVAD implantation in addition to benefits of sternal sparing avoids dilatation of right ventricle and reduces chances of right ventricular failure requiring temporary right ventricular assist.

Comparison of temporary ventricular assist devices and extracorporeal life support in post-cardiotomy cardiogenic shock.

OBJECTIVES: Post-cardiotomy cardiogenic shock (PCCS) results in substantial morbidity and mortality, whereas refractory cases require mechanical circulatory support (MCS). The aim of the study was to compare extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (VADs) utilized in the management of PCCS. METHODS: In total, 56 consecutive patients who developed PCCS from 2005 to 2014 required MCS as a bridge to decision-24 were supported with a VAD and 32 with an ECMO. Groups were compared with respect to pre- and intraoperative characteristics and early and long-term outcomes to evaluate the impact of the type of MCS on complications and survival. Data are mean ± standard deviation and median with quartiles. RESULTS: EuroSCORE II was significantly higher in the VAD group than in the ECMO group (28 ± 20 vs 13 ± 16, P = 0.020) corresponding to significantly higher New York Heart Association (P = 0.031) class and Canadian Cardiovascular Society class (P = 0.040) in the cohort. The median duration of support was 10 (4-23) and 7 (4-10) days in the VAD and ECMO groups, respectively. There were no significant differences in ITU (P = 0.262), hospital stay (P = 0.193) and incidences of most postoperative complications. A significantly higher proportion of patients was successfully weaned/upgraded in the VAD group [13 (54%) vs 4 (13%), P = 0.048] with a trend towards higher discharge rate [9 (38%) vs 5 (16%), P = 0.061]. Overall cumulative survival in early follow-up [Breslow (Generalized Wilcoxon) P = 0.017] and long-term follow-up [Log-rank (Mantel-Cox) p = 0.015] was significantly better in the VAD group. CONCLUSIONS: VAD and ECMO represent essential tools to support patients with PCCS. Our preliminary results might indicate some benefits of using VAD in this group of patients; however, this evidence should be further assessed in larger multicentre trials.

Direct Heart Procurement After Donation After Circulatory Death With Ex Situ Reperfusion.

The most extended technique of heart procurement from donors after circulatory death involves direct procurement and reperfusion in an ex situ normothermic platform using the Organ Care System (TransMedics, Inc, Andover, MA). This report describes a modified technique (at the Harefield Hospital, London, United Kingdom) with rapid donor blood drainage using a cell-saving device and synchronized perfusion on the Organ Care System.

Suicidal hanging donors for lung transplantation: Is this chapter still closed? Midterm experience from a single center in United Kingdom.

In the context of limited donor pool in cardiothoracic transplantation, utilization of organs from high risk donors, such as suicidal hanging donors, while ensuring safety, is under consideration. We sought to evaluate the outcomes of lung transplantations (LTx) that use organs from this group.Between January 2011 and December 2015, 265 LTx were performed at our center. Twenty-two recipients received lungs from donors after suicidal hanging (group 1). The remaining 243 transplantations were used as a control (group 2). Analysis of recipient and donor characteristics as well as outcomes was performed.No statistically significant difference was found in the donor characteristics between analyzed groups, except for higher incidence of cardiac arrest, younger age and smoking history of hanging donors (P < .001, P = .022 and P = .0042, respectively). Recipient preoperative and perioperative characteristics were comparable. Postoperatively in group 1 there was a higher incidence of extracorporeal life support (27.3 vs 9.1%, P = .019). There were no significant differences in chronic lung allograft dysfunction-free survival between group 1 and 2: 92.3 vs 94% at 1 year and 65.9 vs 75.5% at 3 years (P = .99). The estimated cumulative survival rate was also similar between groups: 68.2 vs 83.2% at 1 year and 68.2% versus 72% at 3 years (P = .3758).Hanging as a donor cause of death is not associated with poor mid-term survival or chronic lung allograft dysfunction following transplantation. These results encourage assessment of lungs from hanging donors, and their consideration for transplantation.

Current approaches in retrieval and heart preservation.

Fifty years after the first successful heart transplantation, despite multiple advances in the treatment of advanced acute and chronic heart failure, there is still no equivalent to heart transplantation as a long-term treatment for end-stage heart failure. Transplantation is, however, limited by the scarcity and quality of heart allografts. Donors are nowadays significantly older, particularly in European countries, and traumatic head injury as the cause of death has been replaced by intracerebral hemorrhage or hypoxic brain damage in the majority of cases. In addition, many donors have undergone extensive resuscitation efforts. Recipient characteristics have progressively changed too within the last couple of decades; recipients are older, often with comorbidities and nearly half of them are bridged to transplant with a wide variety of mechanical circulatory support devices. These developments have resulted in heart transplant surgery becoming significantly more challenging with longer more complex surgery and increased ischemia times for organs that were previously considered to be borderline or non-transplantable in many cases. To address this, several options have been explored within the last years and as a result, novel strategies have been developed and tested in order to optimize graft preservation and potentially increase the donor pool. The two notable developments are the ability to procure hearts from donors after circulatory death and the advent of ex-vivo perfusion of hearts. This technology has made the transplantation of extended criteria organs, including those from circulatory determined death (DCD) donors possible, and allow for out of body time of more than 12 hours in heart transplantation. In this review, we set out the basis of the current practices in organ procurement, and the opportunities for the future as demands for organ transplantation continue to increase.