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1.
Biomark Med ; 16(8): 599-611, 2022 06.
Article in English | MEDLINE | ID: mdl-35322701

ABSTRACT

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.


Subject(s)
Heart Transplantation , Hyperlactatemia , Heart Transplantation/adverse effects , Humans , Lactic Acid , Prognosis , Retrospective Studies
2.
ESC Heart Fail ; 9(2): 1400-1412, 2022 04.
Article in English | MEDLINE | ID: mdl-35128823

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 ß receptor (TGF-ßR) 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-ßR blocker. The LMS platform allows the study of mechanosensitive molecular mechanisms of myocardial fibrosis and can lead to the development of novel therapeutic strategies.


Subject(s)
Cardiomyopathies , Mechanotransduction, Cellular , Animals , Cardiomyopathies/pathology , Fibrosis , Humans , Myocardium/pathology , Rats , Rats, Sprague-Dawley
3.
Article in English | MEDLINE | ID: mdl-34662005

ABSTRACT

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.


Subject(s)
Heart Failure , Heart-Assist Devices , Heart Failure/surgery , Humans , Male , Middle Aged , Prosthesis Implantation , Sternum , Thoracotomy , Treatment Outcome
4.
Neurol Clin Pract ; 11(1): e46-e47, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33968494
5.
Article in English | MEDLINE | ID: mdl-33904268

ABSTRACT

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.


Subject(s)
Donor Selection/methods , Extracorporeal Circulation/methods , Lung Transplantation , Lung/physiology , Organ Preservation/methods , Perfusion/methods , Humans , Lung/pathology , Lung/physiopathology , Male , Middle Aged , Tissue Donors
6.
Ann Thorac Surg ; 112(5): 1687-1697, 2021 11.
Article in English | MEDLINE | ID: mdl-33309728

ABSTRACT

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.


Subject(s)
Heart-Assist Devices , Prosthesis Implantation/methods , Thoracotomy/methods , Humans , Prosthesis Design
7.
Ann Thorac Surg ; 111(2): 511-518, 2021 02.
Article in English | MEDLINE | ID: mdl-32698021

ABSTRACT

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.


Subject(s)
Glomerular Filtration Rate , Heart Failure/therapy , Heart-Assist Devices , Adult , Aged , Female , Heart Failure/mortality , Heart Failure/physiopathology , Humans , Male , Middle Aged , Retrospective Studies
8.
J Heart Lung Transplant ; 39(12): 1372-1379, 2020 12.
Article in English | MEDLINE | ID: mdl-32917479

ABSTRACT

BACKGROUND: Heart transplantation is limited by the scarcity of suitable donors. Patients with advanced biventricular failure may require biventricular support to provide optimal cardiac output and end-organ perfusion. We highlight the outcomes of using the HeartWare HVAD System (HVAD) in a biventricular configuration. METHODS: This retrospective study included patients implanted with HVAD as a biventricular assist device (BiVAD) between 2009 and 2017 at 12 participating centers. When used as a right ventricular assist device (VAD) (RVAD), the HVAD can be attached to the right ventricle (RV) or the right atrium (RA). Kaplan-Meier survival estimates were calculated comparing the 2 RVAD implant locations. Comparisons were also made between the timing of RVAD implantation (primary vs staged) on adverse event (AE) profiles and survival. RESULTS: Among the 93 patients who were implanted with a HVAD BiVAD, Kaplan-Meier survivals at 1-year and 2-year were 56% and 47%, respectively. Survival was independent of the location of the HVAD RVAD implant or whether there was an interval between left VAD and RVAD implantation. The most common AEs were bleeding (35.5%), infection (25.8%), and respiratory failure (20.4%). CONCLUSIONS: This study illustrated similar survival in patients receiving a primary or staged HVAD BiVAD implant at 1 year and 2 years. This study also established that the locations of the RVAD implant (RV or RA) result in similar AE profiles.


Subject(s)
Atrial Function, Right/physiology , Heart Atria/physiopathology , Heart Failure/surgery , Heart Ventricles/physiopathology , Heart-Assist Devices , Ventricular Function, Right/physiology , Follow-Up Studies , Global Health , Heart Failure/mortality , Heart Failure/physiopathology , Humans , Retrospective Studies , Survival Rate/trends , Treatment Outcome
9.
Cardiovasc Revasc Med ; 20(11S): 63-66, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31326257

ABSTRACT

In patients with cardiogenic shock, the global use of percutaneous mechanical circulatory support using the Impella CP device has increased with early data suggesting potential benefits over conservative management. In the current case report we describe a simple technique facilitating percutaneous Impella CP or RP exchange with preservation of transfemoral access, which does not require the use of a 0.035' wire. This technique allows for percutaneous sealing of the 14F arteriotomy using new closure devices avoiding the traditional cut-down.


Subject(s)
Anterior Wall Myocardial Infarction/complications , Catheterization, Peripheral , Device Removal , Femoral Artery , Heart-Assist Devices , Prosthesis Implantation/instrumentation , ST Elevation Myocardial Infarction/complications , Shock, Cardiogenic/therapy , Ventricular Function, Left , Anterior Wall Myocardial Infarction/diagnosis , Anterior Wall Myocardial Infarction/physiopathology , Hemostatic Techniques/instrumentation , Humans , Male , Middle Aged , Punctures , Recovery of Function , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/physiopathology , Shock, Cardiogenic/diagnosis , Shock, Cardiogenic/etiology , Shock, Cardiogenic/physiopathology , Treatment Outcome , Vascular Closure Devices
10.
J Thorac Dis ; 11(Suppl 6): S929-S937, 2019 Apr.
Article in English | MEDLINE | ID: mdl-31183172

ABSTRACT

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.

12.
Transplantation ; 103(2): 336-343, 2019 02.
Article in English | MEDLINE | ID: mdl-29757910

ABSTRACT

BACKGROUND: Heart transplantation (HTx) remains the most effective long-term treatment for advanced heart failure. Primary graft dysfunction (PGD) continues to be a potentially life-threatening early complication. In 2014, a consensus statement released by International Society for Heart and Lung Transplantation (ISHLT) established diagnostic criteria for PGD. We studied the incidence of PGD across the United Kingdom. METHODS: We analyzed the medical records of all adult patients who underwent HTx between October 2012 and October 2015 in the 6 UK heart transplant centers Preoperative donor and recipient characteristics, intraoperative details, and posttransplant complications were compared between the PGD and non-PGD groups using the ISHLT definition. Multivariable analysis was performed using logistic regression. RESULTS: The incidence of ISHLT PGD was 36%. Thirty-day all-cause mortality in those with and without PGD was 31 (19%) versus 13 (4.5%) (P = 0.0001). Donor, recipient, and operative factors associated with PGD were recipient diabetes mellitus (P = 0.031), recipient preoperative bilateral ventricular assist device (P < 0.001), and preoperative extracorporeal membranous oxygenation (P = 0.023), female donor to male recipient sex mismatch (P = 0.007), older donor age (P = 0.010), and intracerebral haemorrhage/thrombosis in donor (P = 0.023). Intraoperatively, implant time (P = 0.017) and bypass time (P < 0.001) were significantly longer in the PGD cohort. Perioperatively, patients with PGD received more blood products (P < 0.001). Risk factors identified by multivariable logistic regression were donor age (P = 0.014), implant time (P = 0.038), female: male mismatch (P = 0.033), recipient diabetes (P = 0.051) and preoperative ventricular assist device/extracorporeal membranous oxygenation support (P = 0.012). CONCLUSIONS: This is the first national study to examine the incidence and significance of PGD after HTx using the ISHLT definition. PGD remains a frequent early complication of HTx and is associated with increased mortality.


Subject(s)
Heart Transplantation/adverse effects , Primary Graft Dysfunction/epidemiology , Adult , Blood Transfusion , Female , Heart-Lung Transplantation , Humans , Incidence , Logistic Models , Male , Middle Aged , Primary Graft Dysfunction/etiology , Primary Graft Dysfunction/mortality , Primary Graft Dysfunction/therapy , Retrospective Studies , Risk Factors , United Kingdom
13.
Eur Heart J Cardiovasc Imaging ; 20(2): 199-208, 2019 02 01.
Article in English | MEDLINE | ID: mdl-29668926

ABSTRACT

Aims: The need for right ventricular assist device (RVAD) support after left ventricular assist device (LVAD) therapy is associated with increased morbidity and mortality. We used 2D echocardiographic strain analysis to assess right atrial (RA) and right ventricular (RV) mechanics and predict the need for RV mechanical support after LVAD implantation. Methods and results: Seventy advanced chronic heart failure (ACHF) patients [59 male, age 47 ± 12 years, 79% dilated cardiomyopathy, left ventricular ejection fraction 23 ± 10%] received continuous-flow LVAD as a bridge to transplantation over an 18 month period. A retrospective analysis of RV and RA strain and right heart dyssynchrony was performed comparing those requiring RVAD (20%, n = 14) with those who did not (non-RVAD 80%, n = 56). One-year survival was significantly lower in the RVAD group (50% vs. 79%; P < 0.03). Independent predictors of RVAD support were: low peak RA longitudinal strain (RALS) [odds ratio (OR) 2.5, 95% confidence interval (95% CI) 1.37-2.0; P = 0.03], low RV free-wall longitudinal strain (RVFWLS) (OR 1.3, 95% CI 1.03-2.3; P = 0.04), and degree of intra-RV dyssynchrony (DRVFW-IVS, OR 1.3, 95% CI 1.02-1.3; P = 0.04). Conclusion: In LVAD recipients needing RVAD support, there was lower RALS and RVFWLS in addition to greater RV free-wall mechanical delay. We conclude that RA and RV strain and dyssynchrony analysis have the potential to add incremental value to the pre-VAD-implantation assessment made using conventional echo measurements.


Subject(s)
Echocardiography/methods , Heart Atria/diagnostic imaging , Heart Failure/diagnostic imaging , Heart Failure/physiopathology , Heart Failure/therapy , Heart-Assist Devices , Ventricular Dysfunction, Right/diagnostic imaging , Female , Heart Atria/physiopathology , Humans , Male , Middle Aged , Retrospective Studies , Ventricular Dysfunction, Right/physiopathology
14.
Artif Organs ; 42(12): 1125-1131, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30443997

ABSTRACT

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.


Subject(s)
Heart-Assist Devices , Prosthesis Implantation/methods , Adult , Female , Humans , Male , Middle Aged , Minimally Invasive Surgical Procedures/methods , Minimally Invasive Surgical Procedures/statistics & numerical data , Retrospective Studies , Sternotomy/statistics & numerical data , Thoracotomy/statistics & numerical data
15.
Interact Cardiovasc Thorac Surg ; 27(6): 863-869, 2018 12 01.
Article in English | MEDLINE | ID: mdl-29905854

ABSTRACT

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.


Subject(s)
Cardiac Surgical Procedures/adverse effects , Extracorporeal Membrane Oxygenation/methods , Heart-Assist Devices , Postoperative Complications/therapy , Shock, Cardiogenic/therapy , Adult , Aged , Female , Humans , Incidence , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Shock, Cardiogenic/epidemiology , Shock, Cardiogenic/etiology , United Kingdom/epidemiology
16.
Ann Thorac Surg ; 106(4): e211-e214, 2018 10.
Article in English | MEDLINE | ID: mdl-29752920

ABSTRACT

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.


Subject(s)
Heart Transplantation/methods , Organ Preservation/methods , Perfusion/methods , Tissue Donors , Tissue and Organ Procurement/methods , Humans
17.
Sci Rep ; 8(1): 6947, 2018 05 02.
Article in English | MEDLINE | ID: mdl-29720607

ABSTRACT

The contact cardiac electrogram is derived from the extracellular manifestation of cellular action potentials and cell-to-cell communication. It is used to guide catheter based clinical procedures. Theoretically, the contact electrogram and the cellular action potential are directly related, and should change in conjunction with each other during arrhythmogenesis, however there is currently no methodology by which to concurrently record both electrograms and action potentials in the same preparation for direct validation of their relationships and their direct mechanistic links. We report a novel dual modality apparatus for concurrent electrogram and cellular action potential recording at a single cell level within multicellular preparations. We further demonstrate the capabilities of this system to validate the direct link between these two modalities of voltage recordings.


Subject(s)
Electrophysiological Phenomena , Myocardium/cytology , Myocardium/metabolism , Myocytes, Cardiac/physiology , Action Potentials , Cardiac Electrophysiology , Cells, Cultured , Electrocardiography , Heart/physiology , Humans , Microelectrodes
18.
Lancet Respir Med ; 6(5): 357-367, 2018 05.
Article in English | MEDLINE | ID: mdl-29650408

ABSTRACT

BACKGROUND: Severe primary graft dysfunction (PGD) of grade 3 (PGD3) is a common serious complication following lung transplantation. We aimed to assess physiological donor lung preservation using the Organ Care System (OCS) Lung device compared with cold static storage. METHODS: In this non-inferiority, randomised, controlled, open-label, phase 3 trial (INSPIRE) recipients were aged 18 years or older and were registered as standard criteria primary double lung transplant candidates. Eligible donors were younger than 65 years old with a ratio of partial pressure of oxygen in arterial blood to the fraction of inspired oxygen of more than 300 mm Hg. Transplant recipients were randomly assigned (1:1) with permuted blocks, stratified by centre, to receive standard criteria donor lungs preserved in the OCS Lung device (OCS arm) or cold storage at 4°C (control arm). The composite primary effectiveness endpoint was absence of PGD3 within the first 72 h after transplant and 30-day survival in the per-protocol population, with a stringent 4% non-inferiority margin. Superiority was tested upon meeting non-inferiority. The primary safety endpoint was the mean number of lung graft-related serious adverse events within 30 days of transplant. We did analyses in the per-protocol and intention-to-treat populations. This trial is registered with ClinicalTrials.gov, number NCT01630434. FINDINGS: Between Nov 17, 2011, and Nov 24, 2014, we randomly assigned 370 patients, and 320 (86%) underwent transplantation (n=151 OCS and n=169 control); follow-up was completed in Nov 24, 2016. The primary endpoint was met in 112 (79·4%) of 141 patients (95% CI 71·8 to 85·8) in the OCS group compared with 116 (70·3%) of 165 patients (62·7 to 77·2) in the control group (non-inferiority point estimate -9·1%; 95% CI -∞ to -1·0; p=0·0038; and superiority test p=0·068). Patient survival at day 30 post-transplant was 135 (95·7%) of 141 patients (95% CI 91·0-98·4) in the OCS group and 165 patients (100%; 97·8-100·0) in the control group (p=0·0090) and at 12 months was 126 (89·4%) of 141 patients (83·1-93·9) for the OCS group compared with 146 (88·1%) of 165 patients (81·8-92·8) for the control group. Incidence of PGD3 within 72 h was reported in 25 (17·7%) of 141 patients in the OCS group (95% CI 11·8 to 25·1) and 49 (29·7%) of 165 patients in the control group (22·8 to 37·3; superiority test p=0·015). The primary safety endpoint was met (0·23 lung graft-related serious adverse events in the OCS group compared with 0·28 events in the control group [point estimate -0·045%; 95% CI -∞ to 0·047; non-inferiority test p=0·020]). In the intention-to-treat population, causes of death at 30 days and in hospital were lung graft failure or lung infection (n=2 for OCS vs n=7 for control), cardiac causes (n=4 vs n=1), vascular or stroke (n=3 vs n=0), metabolic coma (n=0 vs n=2), and generalised sepsis (n=0 vs n=1). INTERPRETATION: The INSPIRE trial met its primary effectiveness and safety endpoints. Although no short-term survival benefit was reported, further research is needed to see whether the reduced incidence of PGD3 within 72 h of a transplant might translate into earlier recovery and improved long-term outcomes after lung transplantation. FUNDING: TransMedics Inc.


Subject(s)
Lung Transplantation/methods , Organ Preservation/instrumentation , Primary Graft Dysfunction/prevention & control , Adult , Cryopreservation/methods , Female , Humans , Lung Transplantation/adverse effects , Male , Middle Aged , Organ Preservation Solutions , Prospective Studies , Risk Factors , Survival Analysis , Treatment Outcome
19.
Ann Cardiothorac Surg ; 7(1): 67-74, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29492384

ABSTRACT

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.

20.
ASAIO J ; 64(5): 636-642, 2018.
Article in English | MEDLINE | ID: mdl-29373336

ABSTRACT

Partial circulatory support is a promising concept for the treatment of heart failure patients. A better understanding of induced hemodynamic changes is essential for optimizing treatment efficacy. Computational fluid dynamics (CFD) is an alternative method to gain insight into flow phenomena difficult to obtain in vivo. In 10 patients implanted with a Circulite Synergy Micro-pump (HeartWare, Framingham, Massachusetts) (a continuous flow partial circulatory assist device connecting the left atrium to the right subclavian artery), transient CFD simulations were performed. Patients were divided into two groups depending on their cardiac output (CO; high CO group: 5.5 ± 1.1 L/min, low CO group: 1.7 ± 0.7 L/min). The partial assist device provided a supporting flow of 1.5 ± 0.8 L/min. Support was highest at diastole and decreased during systole because of a collision of the blood flows from the partial assist device and the CO. Reversed flow counteracting the flow of the device was significantly higher for the high CO group (mean flow in peak systole: -2.18 ± 1.08 vs. 0.23 ± 0.59 L/min; p = 0.002) showing an inverse correlation between CO and amount of reversed flow during peak systole (R = -0.7; p < 0.02). The flow collision lead to higher total pressures at the point of collision and consequently in the Circulite outflow graft. The CFD simulations allow quantifying hemodynamic alterations in patients with partial support consisting of a flow collision, thereby reducing effectiveness of the circulatory support. Partial support in heart failure patients alternates their hemodynamics not only in providing support for the circulation but also inducing unfavorable changes in flow patterns.


Subject(s)
Cardiac Output/physiology , Heart Failure/physiopathology , Heart-Assist Devices , Hemodynamics/physiology , Cardiovascular System/physiopathology , Female , Heart Failure/therapy , Humans , Hydrodynamics , Male , Treatment Outcome
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