Heart Transplantation From DCD Donors in Australia: Lessons Learned From the First 74 Cases.

Heart transplantation from donation after circulatory death (DCD) donors has the potential to substantially increase overall heart transplant activity. The aim of this report is to review the first 8 y of our clinical heart transplant program at St Vincent's Hospital Sydney, to describe how our program has evolved and to report the impact that changes to our retrieval protocols have had on posttransplant outcomes. Since 2014, we have performed 74 DCD heart transplants from DCD donors utilizing a direct procurement protocol followed by normothermic machine perfusion. Changes to our retrieval protocol have resulted in a higher retrieval rate from DCD donors and fewer rejections of DCD hearts during normothermic machine perfusion. Compared with our previously reported early experience in the first 23 transplants, we have observed a significant reduction in the incidence of severe primary graft dysfunction from 35% (8/23) to 8% (4/51) in the subsequent 51 transplant recipients ( P < 0.01). The only withdrawal time interval significantly associated with severe primary graft dysfunction was the asystolic warm ischemic time: 15 (12-17) versus 13 (11-14) min ( P < 0.05). One- and 5-y survival of DCD heart transplant recipients was 94% and 88%, comparable to that of a contemporary cohort of donation after brain death recipients: 87 and 81% ( P -value was not significant). In conclusion, heart transplantation from DCD donors has become a major contributor to our overall transplant activity accounting for almost 30% of all transplants performed by our program in the last 2 y, with similar DCD and donation after brain death outcomes.

Comparing left ventricular assist device inflow cannula angle between median sternotomy and thoracotomy using 3D reconstructions.

BACKGROUND: Left ventricular assist device (LVAD) implantation via thoracotomy has many potential advantages compared to conventional sternotomy, including improved inflow cannula (IFC) positioning. We compared the difference in IFC angles, postoperative, and long-term outcomes for patients with LVADs implanted via thoracotomy and sternotomy. METHODS: A single-center, retrospective analysis of 14 patients who underwent thoracotomy implantation was performed and matched with 28 patients who underwent sternotomy LVAD implantations for a total of 42 patients. Inclusion required a minimum LVAD support duration of 30 days and excluded concomitant procedures. A postoperative CT-chest was used to measure the angle the between the IFC and mitral valve in two-dimensions and results were compared with three-dimensional reconstruction using the same CT chest. Outcome data were extracted from medical records. RESULTS: There was no significant difference in gender, INTERMACS score, BMI, or age between the two groups. Median cardiopulmonary bypass time was longer in the thoracotomy group compared to the sternotomy group, 107 min (86-122) versus 76 min (56-93), p < 0.01. 3D reconstructions revealed less deviation of the IFC away from the mitral valve in devices implanted via thoracotomy compared to sternotomy, median (IQR) angle 16.3° (13.9°-21.0°) versus 23.2° (17.9°-26.4°), p < 0.01. Rates of pump thrombosis, stroke, and gastrointestinal bleeding were not significantly different. CONCLUSIONS: Devices implanted via thoracotomy demonstrated less deviation away from mitral valve. However, there was no difference in morbidity between the two approaches. 3D reconstruction of the heart is an innovative technique to measure angulation and is clinically advantageous when compared to 2D imaging.

Anatomical human fitting of the BiVACOR total artificial heart.

BACKGROUND: BiVACOR is a novel total artificial heart (TAH) utilizing a single centrifugal magnetically levitated rotor with the ability to modulate pulsatile flow. The device has been successfully tested in a bovine model. We undertook a multicenter anatomical and virtual fitting study of the BiVACOR in patients undergoing heart transplantation. METHODS: 10 patients were recruited across two heart transplant centers. A sterilized 1:1 titanium model of the device was inserted into the patient's chest post heart explant, prior to implantation of the donor heart. Measurements were recorded in situ. The device was then removed. Following this, retrospective 3D reconstructions were created from computed tomography chest scans to simulate a virtual fitting. RESULTS: Mean age was 53 years (range 38-67). Mean BMI was 28 (range 20-37). Heart failure etiology was varied-with ischemic cardiomyopathy being the most common. Mean spine-to-sternum distance at the tenth thoracic vertebrae (T10) was 14 cm (range 11-18). Mean aorta to aortic Port distance was 0.2 cm (range 0-0.5). Mean pulmonary artery to pulmonary artery port distance was 4.2 cm (range 1-7). The device fitted suitably in all patients without gross distortion to the geometry between native vessel/chamber and port. CONCLUSIONS: This study described the anatomical and virtual fitting of the BiVACOR TAH. The device fit well within the chest cavities of all 10 patients, who represented a variety of body morphologies and heart failure etiology.

The impact of frailty on mortality after heart transplantation.

BACKGROUND: Frailty is prevalent in the patients with advanced heart failure; however, its impact on clinical outcomes after heart transplantation (HTx) is unclear. The aim of this study was to assess the impact of pre-transplant frailty on mortality and the duration of hospitalization after HTx. METHODS: We retrospectively reviewed the post-transplant outcomes of 140 patients with advanced heart failure who had undergone frailty assessment within the 6-month interval before HTx: 43 of them were frail (F) and 97 were non-frail (NF). RESULTS: Post-transplant survival rates for the NF cohort at 1 and 12 months were 97% (93-100) and 95% (91-99) (95% CI), respectively. In contrast, post-transplant survival rates for the F cohort at the same time points were 86% (76-96) and 74% (60-84) (p < 0.0008 vs NF cohort), respectively. The Cox proportional hazards regression analysis demonstrated that pre-transplant frailty was an independent predictor of post-transplant mortality with a hazard ratio of 3.8 (95% CI: 1.4-10.5). Intensive care unit and hospital length of stay were 2 and 7 days longer in the F cohort (both p < 0.05), respectively, than in the NF cohort. CONCLUSIONS: Frailty within 6 months before HTx is independently associated with increased mortality and prolonged hospitalization after transplantation. Future research should focus on the development of strategies to mitigate the adverse effects of pre-transplant frailty.

DCD donations and outcomes of heart transplantation: the Australian experience.

PURPOSE: There is increasing clinical utilization of hearts from the donation after circulatory death (DCD) pathway with the aim of expanding the donor pool and mitigating the ever-present discrepancy between the inadequate availability of good quality donor hearts and the rising number of patients with end-stage heart failure. METHODS: This article reviews the rationale, practice, logistical factors, and 5-year experience of DCD heart transplantation at St Vincent's Hospital, Sydney. FINDINGS: Between July 2014 and July 2019, 69 DCD donor retrievals were undertaken resulting in 49 hearts being instrumented on an ex situ normothermic cardiac perfusion device. Seventeen (35%) of these hearts were declined and the remaining 32 (65%) were used for orthotopic DCD heart transplantation. At 5 years of follow-up, the 1-, 3-, and 5-year survival was 96%, 94%, and 94% for DCD hearts compared with 89%, 83%, and 82% respectively for donation after brain death (DBD) hearts (n.s). The immediate post-implant requirement for temporary extra-corporeal membrane oxygenation (ECMO) support for delayed graft function was 31% with no difference in rejection rates when compared with the contemporaneous cohort of patients transplanted with standard criteria DBD hearts. SUMMARY: DCD heart transplantation has become routine and incorporated into standard clinical practice by a handful of pioneering clinical transplant centres. The Australian experience demonstrates that excellent medium-term outcomes are achievable from the use of DCD hearts. These outcomes are consistent across the other centres and consequently favour a more rapid and wider uptake of heart transplantation using DCD donor hearts, which would otherwise be discarded.

Outcomes of Donation After Circulatory Death Heart Transplantation in Australia.

BACKGROUND: Transplantation of hearts retrieved from donation after circulatory death (DCD) donors is an evolving clinical practice. OBJECTIVES: The purpose of this study is to provide an update on the authors' Australian clinical program and discuss lessons learned since performing the world's first series of distantly procured DCD heart transplants. METHODS: The authors report their experience of 23 DCD heart transplants from 45 DCD donor referrals since 2014. Donor details were collected using electronic donor records (Donate Life, Australia) and all recipient details were collected from clinical notes and electronic databases at St. Vincent's Hospital. RESULTS: Hearts were retrieved from 33 of 45 DCD donors. A total of 12 donors did not progress to circulatory arrest within the pre-specified timeframe. Eight hearts failed to meet viability criteria during normothermic machine perfusion, and 2 hearts were declined due to machine malfunction. A total of 23 hearts were transplanted between July 2014 and April 2018. All recipients had successful implantation, with mechanical circulatory support utilized in 9 cases. One case requiring extracorporeal membrane oxygenation subsequently died on the sixth post-operative day, representing a mortality of 4.4% over 4 years with a total follow-up period of 15,500 days for the entire cohort. All surviving recipients had normal cardiac function on echocardiogram and no evidence of acute rejection on discharge. All surviving patients remain in New York Heart Association functional class I with normal biventricular function. CONCLUSIONS: DCD heart transplant outcomes are excellent. Despite a higher requirement for mechanical circulatory support for delayed graft function, primarily in recipients with ventricular assist device support, overall survival and rejection episodes are comparable to outcomes from contemporary brain-dead donors.

Nosocomial infections acquired by patients treated with extracorporeal membrane oxygenation.

BACKGROUND: Infectious complications in patients treated with extracorporeal membrane oxygenation (ECMO) are a frequent contributor to morbidity and mortality in this group. Defining the characteristics of ECMO-related infections may inform treatment decisions, including antimicrobial therapy. METHODS: A retrospective observational study in an Australian intensive care unit, including adult patients treated with ECMO for at least 48 hours, over a 3-year period. Medical records were analysed for evidence of bloodstream infections (BSIs) and wound infections (WIs) at the ECMO cannulation site or the sternum. Demographic, ECMO-related and clinical data were collected, including inpatient antibiotic usage. RESULTS: We included 98 patients in the study. The median age was 50 years (IQR, 39-57 years). The median duration of ECMO treatment was 6.6 days (IQR, 4.0-12.8 days). Twenty-four infections were diagnosed in 21 patients; eight patients were diagnosed with BSIs on ECMO, 14 developed cannulation-site WIs, and two patients developed sternal wound infections. On multivariate analysis, we found that factors that increased infection risk included immunosuppression (OR, 2.9; P = 0.04) and treatment with venoarterial (VA) ECMO (OR, 14.7; P = 0.01). Infected patients had a significantly longer duration of hospital admission than patients without BSI or WI (55 days v 30 days; P = 0.03). Prior antibiotic use did not appear to be protective against subsequent infection. CONCLUSIONS: Infectious complications are common in ECMO patients and are associated with longer durations of hospital admission. Isolated pathogens were predominantly hospital-acquired Gram-negative bacteria and yeasts. Immunosuppression and treatment with VA ECMO were found to be specific risk factors for infection.

Long distance heart transplantation: a tale of two cities.

In this 'paired' case report, we describe two heart transplants performed 3 days apart at our centre. Both cases involved very prolonged transportation time of the donor heart. In one case, the donor heart was transported in an ice chest, while in the other case the organ was transported using a normothermic ex vivo perfusion (NEVP) system. The additional retrieval costs incurred by the use NEVP were more than offset by the reduction in subsequent inpatient costs.

Primary percutaneous coronary intervention for inferior ST-segment elevation myocardial infarction in a patient supported by the HeartWare left ventricular assist device.

A 63-year-old man with an ischaemic cardiomyopathy, supported by the HeartWare left ventricular assist device (LVAD), presented with ventricular tachycardia and inferior ST-elevation myocardial infarction (STEMI) with associated acute right ventricular (RV) dysfunction. He underwent primary percutaneous coronary intervention with balloon angioplasty and placement of three drug-eluting stents in the proximal-to-mid right coronary artery. Post-procedure, ventricular arrhythmias abated, RV systolic dysfunction resolved and RV size normalised. Percutaneous coronary intervention (PCI) facilitated by the use of miniaturised percutaneous LVAD has become an increasingly available treatment option for high-risk patients. PCI in patients on established full mechanical circulatory support is not a common occurrence. Indeed, to our knowledge, this is the first case of primary percutaneous coronary intervention on an LVAD-supported heart reported in the medical literature. The case raises several specific issues that are of peculiar interest to clinicians involved in the care of patients supported by mechanical assist devices who experience an acute coronary syndrome requiring emergent revascularisation.

Reversibility of Frailty After Bridge-to-Transplant Ventricular Assist Device Implantation or Heart Transplantation.

BACKGROUND: We recently reported that frailty is independently predictive of increased mortality in patients with advanced heart failure referred for heart transplantation (HTx). The aim of this study was to assess the impact of frailty on short-term outcomes after bridge-to-transplant ventricular assist device (BTT-VAD) implantation and/or HTx and to determine if frailty is reversible after these procedures. METHODS: Between August 2013 and August 2016, 100 of 126 consecutive patients underwent frailty assessment using Fried's Frailty Phenotype before surgical intervention: 40 (21 nonfrail, 19 frail) BTT-VAD and 77 (60 nonfrail, 17 frail) HTx-including 17 of the 40 BTT-VAD supported patients. Postprocedural survival, intubation time, intensive care unit, and hospital length of stay were compared between frail and nonfrail groups. Twenty-six frail patients were reassessed at 2 months or longer postintervention. RESULTS: Frail patients had lower survival (63 ± 10% vs 94 ± 3% at 1 year, P = 0.012) and experienced significantly longer intensive care unit (11 vs 5 days, P = 0.002) and hospital (49 vs 25 days, P = 0.003) length of stay after surgical intervention compared with nonfrail patients. Twelve of 13 frail patients improved their frailty score after VAD (4.0 ± 0.8 to 1.4 ± 1.1, P < 0.001) and 12 of 13 frail patients improved their frailty score after HTx (3.2 ± 0.4 to 0.9 ± 0.9, P < 0.001). Handgrip strength and depression improved postintervention. Only a slight improvement in cognitive function was seen postintervention. CONCLUSIONS: Frail patients with advanced heart failure experience increased mortality and morbidity after surgical intervention with BTT-VAD or HTx. Among those who survive frailty is partly or completely reversible underscoring the importance of considering this factor as a dynamic not fixed entity.

Extracorporeal heart perfusion before heart transplantation: the heart in a box.

PURPOSE OF REVIEW: Cold static storage is a time-tested and simple method of preserving hearts retrieved from optimal donors after brain death (DBD). The increasing gap between supply and demand for donor organs together with changing donor and recipient characteristics have led to renewed interest in the use of machine perfusion to increase both the quality and quantity of donor hearts for transplantation. RECENT FINDINGS: Two major approaches to machine perfusion of donor hearts have been investigated - hypothermic (HMP) and normothermic machine perfusion (NMP). Recent preclinical studies with HMP confirm that it provides superior donor heart preservation to cold static storage. HMP systems have been developed for human heart preservation but have yet to be tested clinically. In contrast, NMP has undergone extensive clinical evaluation in human heart transplantation, including optimal and higher risk DBD donors. In addition, NMP has enabled distant procurement and successful transplantation of hearts retrieved from human donation after circulatory death donors. SUMMARY: Initial clinical experience suggests that NMP of donor hearts retrieved from higher risk DBD and donation after circulatory death donors enables well tolerated ex-vivo reanimation, preservation, and assessment of these organs. In particular, this technology allows successful utilization of extended-criteria donor hearts that would otherwise be discarded.

Long-term biventricular HeartWare ventricular assist device support--Case series of right atrial and right ventricular implantation outcomes.

BACKGROUND: There is limited information on outcomes using the HeartWare ventricular assist device (HVAD; HeartWare, Framington, MA) as a biventricular assist device, especially with respect to site of right ventricular assist device (RVAD) implantation. METHODS: Outcomes in 13 patients with dilated cardiomyopathy and severe biventricular failure who underwent dual HVAD implantation as bridge to transplantation between August 2011 and October 2014 were reviewed. RESULTS: Of 13 patients, 10 were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Level 1, and 3 were INTERMACS Level 2. Mean age was 45 ± 11 years, and mean body mass index was 26 ± 4 kg/m(2). There were 7 patients on temporary mechanical support pre-operatively (extracorporeal life support, n = 5; intra-aortic balloon pump, n = 2). The median hospital length of stay was 53 days (interquartile range [IQR] 33-70 days) with a median intensive care unit length of stay of 14 days (IQR 8-36 days). The median length of support on device was 269 days (IQR 93-426 days). The right HVAD was implanted in the right ventricular (RV) free wall in 6 patients and in the right atrial (RA) free wall in 7 patients. Transplantation was successfully performed in 5 patients, and overall survival for the entire cohort was 54%. RVAD pump thrombosis occurred in 3 of 6 RV pumps and 1 of 7 RA pumps. No left ventricular assist device pump thrombosis was observed. Bleeding tended to be higher in the RV implantation group (3 of 6 vs 0 of 7). During follow up, 6 patients died (4 of 7 in the RA group vs 2 of 6 in the RV group). Cause of death was multiple-organ failure in 3 patients, sepsis in 2 patients, and intracerebral hemorrhage in 1 patient. CONCLUSIONS: Critically ill patients who require biventricular support can be successfully bridged to transplant using 2 HVADs. RA implantation may allow right heart support with lower pump thrombosis and bleeding complications, although this was at the expense of a higher mortality in this cohort.

Adult heart transplantation with distant procurement and ex-vivo preservation of donor hearts after circulatory death: a case series.

BACKGROUND: Orthotopic heart transplantation is the gold-standard long-term treatment for medically refractive end-stage heart failure. However, suitable cardiac donors are scarce. Although donation after circulatory death has been used for kidney, liver, and lung transplantation, it is not used for heart transplantation. We report a case series of heart transplantations from donors after circulatory death. METHODS: The recipients were patients at St Vincent's Hospital, Sydney, Australia. They received Maastricht category III controlled hearts donated after circulatory death from people younger than 40 years and with a maximum warm ischaemic time of 30 min. We retrieved four hearts through initial myocardial protection with supplemented cardioplegia and transferred to an Organ Care System (Transmedics) for preservation, resuscitation, and transportation to the recipient hospital. FINDINGS: Three recipients (two men, one woman; mean age 52 years) with low transpulmonary gradients (<8 mm Hg) and without previous cardiac surgery received the transplants. Donor heart warm ischaemic times were 28 min, 25 min, and 22 min, with ex-vivo Organ Care System perfusion times of 257 min, 260 min, and 245 min. Arteriovenous lactate values at the start of perfusion were 8·3-8·1 mmol/L for patient 1, 6·79-6·48 mmol/L for patient 2, and 7·6-7·4 mmol/L for patient 3. End of perfusion lactate values were 3·6-3·6 mmol/L, 2·8-2·3 mmol/L, and 2·69-2·54 mmol/L, respectively, showing favourable lactate uptake. Two patients needed temporary mechanical support. All three recipients had normal cardiac function within a week of transplantation and are making a good recovery at 176, 91, and 77 days after transplantation. INTERPRETATION: Strict limitations on donor eligibility, optimised myocardial protection, and use of a portable ex-vivo organ perfusion platform can enable successful, distantly procured orthotopic transplantation of hearts donated after circulatory death. FUNDING: NHMRC, John T Reid Charitable Trust, EVOS Trust Fund, Harry Windsor Trust Fund.