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.

Organ Donation after Circulatory Determination of Death in India: A Joint Position Paper.

Organ donation following circulatory determination of death (DCDD) has contributed significantly to the donor pool in several countries. In India, majority of deceased donations happen following brain death (BD). While existing legislation allows for DCDD, there have been only few reports of kidney transplantation following DCDD from India. This document, prepared by a multidisciplinary group of experts, reviews international best practices in DCDD and outlines the path for DCDD in India. Ethical, medical, legal, economic, procedural, and logistic challenges unique to India have been addressed. The practice of withdrawal of life-sustaining treatment (WLST) in India, laid down by the Supreme Court of India, is time-consuming, possible only in patients in a permanent vegetative state, and too cumbersome for day-to-day practice. In patients where continued medical care is futile, the procedure for WLST is described. In controlled DCDD (category-III), decision for WLST is independent of and delinked from the subsequent possibility of organ donation. Families that are inclined toward organ donation are explained the procedure including the timing and location of WLST, consent for antemortem measures, no-touch period, and the possibility of stand-down and return to the intensive care unit (ICU) without donation. In donation following neurologic determination of death (DNDD), if cardiac arrest occurs during the process of BD declaration, the protocol for DCDD category-IV has been described in detail. In DCDD category-V, organ donation may be possible following unsuccessful cardiopulmonary resuscitation of cardiac arrest in the ICU. An outline of organ-specific requisites for kidney, liver, heart, and lung transplantation following DCDD and techniques, such as normothermic regional perfusion (nRP) and ex vivo machine perfusion, has been provided. The outcomes of transplantation following DCDD are comparable to those following DBDD or living donor transplantation. Documents and checklists necessary for successful execution of DCDD in India are described. How to cite this article: Seth AK, Mohanka R, Navin S, Gokhale AGK, Sharma A, Kumar A, et al. Organ Donation after Circulatory Determination of Death in India: A Joint Position Paper. Indian J Crit Care Med 2022;26(4):421-438.

Chronic thromboembolic pulmonary hypertension in Australia and New Zealand: An analysis of the PHSANZ registry.

BACKGROUND AND OBJECTIVE: Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious condition occurring in 2%-4% of patients after acute pulmonary embolism. Pulmonary endarterectomy (PEA) is a potential cure for technically operable disease. The epidemiology and long-term outcomes of CTEPH have not been previously described in Australia and New Zealand. METHODS: Data were extracted from the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) registry for patients diagnosed with CTEPH between January 2004 and March 2020. Baseline characteristics, treatment strategies, outcome data and long-term survival are reported. RESULTS: A total of 386 patients were included with 146 (37.8%) undergoing PEA and 240 (62.2%) in the non-PEA group. PEA patients were younger (55 ± 16 vs. 62 ± 16 years, p < 0.001) with higher baseline 6-min walk distance (6MWD; 405 ± 122 vs. 323 ± 146 m, p = 0.021), whilst both groups had similar baseline pulmonary haemodynamics. Pulmonary hypertension-specific therapy was used in 54% of patients post-PEA and 88% in the non-PEA group. The 1-, 3- and 5-year survival rates were 93%, 87% and 84% for the PEA group compared to 86%, 73% and 62%, respectively, for the non-PEA group (p < 0.001). Multivariate survival analysis showed baseline 6MWD was an independent predictor of survival in both operated and medically managed patients. CONCLUSION: In this first multicentre report of CTEPH in Australia and New Zealand, long-term survival is comparable to that in other contemporary CTEPH registries. However, PEA was only performed in a minority of CTEPH patients (37.8%) and significantly less than overseas reports. Greater awareness of PEA and improved patient access to experienced CTEPH centres are important priorities.

The Effect of Increasing Donor Age on Myocardial Ischemic Tolerance in a Rodent Model of Donation After Circulatory Death.

Hearts from older donors or procured via donation after circulatory death (DCD) can alleviate transplant waitlist; however, these hearts are particularly vulnerable to injury caused by warm ischemic times (WITs) inherent to DCD. This study investigates how the combination of increasing donor age and pharmacologic supplementation affects the ischemic tolerance and functional recovery of DCD hearts and how age impacts cardiac mitochondrial respiratory capacity and oxidative phosphorylation. METHODS: Wistar rats (12-, 18-, and 24-mo-old) were subjected to DCD with 20-min fixed WIT. Hearts were procured, instrumented onto a Langendorff perfusion circuit, flushed with Celsior preservation solution with or without supplementation (glyceryl trinitrate [GTN]/erythropoietin [EPO]/zoniporide [Z]) and perfused (Krebs-Henseleit buffer, 37°C Langendorff 30-min, working 30-min). Cardiac functional recovery of aortic flow (AF), coronary flow (CF), cardiac output (CO), and lactate dehydrogenase release were measured. Native heart tissue (3-, 12-, and 24-mo) were assessed for mitochondrial respiratory capacity. RESULTS: Unsupplemented 18- and 24-month DCD hearts showed a 6-fold decrease in AF recovery relative to unsupplemented 12-month DCD hearts. GTN/EPO/Z supplementation significantly increased AF and CO recovery of 18-month DCD hearts to levels comparable to supplemented 12-month hearts; however, GTN/EPO/Z did not improve 24-month DCD heart recovery. Compared to 12-month heart tissue, 24-month hearts exhibited significantly impaired mitochondrial oxygen flux at complex I, II, and uncoupled maximal respiration stage. CONCLUSIONS: Reduced ischemic tolerance after DCD was associated with increasing age. Pharmacologic supplementation improves functional recovery of rat DCD hearts but only up to age 18 months, possibly attributed to a decline in mitochondrial respiratory capacity with increasing age.

Expanding controlled donation after the circulatory determination of death: statement from an international collaborative.

A decision to withdraw life-sustaining treatment (WLST) is derived by a conclusion that further treatment will not enable a patient to survive or will not produce a functional outcome with acceptable quality of life that the patient and the treating team regard as beneficial. Although many hospitalized patients die under such circumstances, controlled donation after the circulatory determination of death (cDCDD) programs have been developed only in a reduced number of countries. This International Collaborative Statement aims at expanding cDCDD in the world to help countries progress towards self-sufficiency in transplantation and offer more patients the opportunity of organ donation. The Statement addresses three fundamental aspects of the cDCDD pathway. First, it describes the process of determining a prognosis that justifies the WLST, a decision that should be prior to and independent of any consideration of organ donation and in which transplant professionals must not participate. Second, the Statement establishes the permanent cessation of circulation to the brain as the standard to determine death by circulatory criteria. Death may be declared after an elapsed observation period of 5 min without circulation to the brain, which confirms that the absence of circulation to the brain is permanent. Finally, the Statement highlights the value of perfusion repair for increasing the success of cDCDD organ transplantation. cDCDD protocols may utilize either in situ or ex situ perfusion consistent with the practice of each country. Methods to accomplish the in situ normothermic reperfusion of organs must preclude the restoration of brain perfusion to not invalidate the determination of death.

Frailty in heart transplantation: Report from the heart workgroup of a consensus conference on frailty.

A consensus conference on frailty in solid organ transplantation took place on February 11, 2018, to discuss the latest developments in frailty, adopt a standardized approach to assessment, and generate ideas for future research. The findings and consensus of the Frailty Heart Workgroup (American Society of Transplantation's Thoracic and Critical Care Community of Practice) are presented here. Frailty is defined as a clinically recognizable state of increased vulnerability resulting from aging-associated decline in reserve and function across multiple physiologic systems such that the ability to cope with every day or acute stressors is compromised. Frailty is increasingly recognized as a distinct biologic entity that can adversely affect outcomes before and after heart transplantation. A greater proportion of patients referred for heart transplantation are older and have more complex comorbidities. However, outcomes data in the pretransplant setting, particularly for younger patients, are limited. Therefore, there is a need to develop objective frailty assessment tools for risk stratification in patients with advanced heart disease. These tools will help to determine appropriate recipient selection for advanced heart disease therapies including heart transplantation and mechanical circulatory support, improve overall outcomes, and help distinguish frailty phenotypes amenable to intervention.

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.

Characterization of infected, explanted ventricular assist device drivelines: The role of biofilms and microgaps in the driveline tunnel.

BACKGROUND: Driveline infections remain a major complication of ventricular assist device (VAD) implantation. This study aimed to characterize in vivo microbial biofilms associated with driveline infections and host tissue integration of implanted drivelines. METHODS: A total of 9 infected and 13 uninfected drivelines were obtained from patients with VAD undergoing heart transplantation in Australia between 2016 and 2018. Each driveline was sectioned into 11 pieces of 1.5 cm in length, and each section was examined by scanning electron microscopy (SEM) and viable counts for microbial biofilms. Microorganisms were cultured and identified. Host tissue integration of clinical drivelines was assessed with micro-computed tomography (CT) and SEM. An in vitro interstitial biofilm assay was used to simulate biofilm migration in the driveline tunnel, and time-lapse microscopy was performed. RESULTS: Of the 9 explanted, infected drivelines, all had organisms isolated from varying depths along the velour section of the drivelines, and all were consistent with the swab culture results of the clinically infected exit site. SEM and micro-CT suggested insufficient tissue integration throughout the driveline velour, with microgaps observed. Clinical biofilms presented as microcolonies within the driveline tunnel, with human tissue as the sub-stratum, and were resistant to anti-microbial treatment. Biofilm migration mediated by a dispersal-seeding mechanism was observed. CONCLUSIONS: This study of explanted infected drivelines showed extensive anti-microbial-resistant biofilms along the velour, associated with microgaps between the driveline and the surrounding tissue. These data support the enhancement of tissue integration into the velour as a potential preventive strategy against driveline infections by preventing biofilm migration that may use microgaps as mediators.

Cardiac donation after circulatory death.

PURPOSE OF REVIEW: Increasing number of patients with end-stage heart failure and those with improved survivorship from selective utilization of implantable mechanical circulatory support devices have added further burden and complexity to the transplant waitlist and on the rate-limiting availability of donor hearts from the standard pathway of donation after brain death. Unlike this conventional route, the increasing clinical use of donation after circulatory death (DCD) donor hearts necessitates a closer understanding of the logistics involved in the DCD process as well as of the risks associated with the unique pathophysiological consequences in this setting. RECENT FINDINGS: Notwithstanding a higher incidence of delayed graft function, the clinical utilization of DCD hearts for cardiac transplantation over the past five years has demonstrated this to be a well-tolerated and strategic alternative with excellent medium-term clinical outcomes. SUMMARY: The uptake of DCD heart transplantation remains selective and currently confined to Australia, the United Kingdom, Belgium, and more recently the USA. A more significant adoption will only come about through: a concerted effort to resolve the ethical and clinical controversies; a better understanding of postconditioning strategies; continued resolve to reduce the obligatory period of warm ischemia; and from better extracorporeal platforms that permit functional viability assessment of the DCD donor heart.

The donor heart and organ perfusion technology.

Recent advancement in organ perfusion technology has led to increase clinical transplantation of marginal donor organs and allow for distant procurement of cardiac allograft beyond the time limitation of cold static storage. Ex-situ heart perfusion also provides essential nutrients to maintain cell integrity, thereby reducing the risk of ischaemic injury for functional preservation and provides a platform to assess organ viability and feasibility, with the potential for pharmacotherapy to recover these hearts. Notably, the use of NMP has led to the first distant procurement cardiac transplantation from a donation after circulatory death (DCD) in 2014, which resulted in the adoption of DCD heart transplantation in 4 centres between the United Kingdom and Australia. To date, over 100 DCD heart transplants have been performed utilising cardiac perfusion system with an estimated 10-15% increase in transplant activity in the individual units. This review aims to provide an overview of current experience and outcomes using cardiac perfusion technology, including future technologies and recent advancement within the field.

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.

Cyclosporine A as a Cardioprotective Agent During Donor Heart Retrieval, Storage, or Transportation: Benefits and Limitations.

BACKGROUND: Storage of donor hearts in cardioplegic solutions supplemented with conditioning agents activating endogenous mitochondrial protective signaling enhanced their postreperfusion recovery. The present study investigates the role of timing and duration of cardiac exposure to cyclosporine A (CsA), another putative mitochondrial protectant, on cardiac functional recovery and potential mechanisms of CsA action in an isolated working rat heart model of donor heart retrieval and storage. METHODS: After measurement of baseline function, hearts were arrested and stored for 6 hours at 4°C in either Celsior alone or Celsior + CsA (0.2 µM), then reperfused for 45 minutes in Krebs solution, when functional recovery was assessed. Two additional groups of Celsior-alone stored hearts were exposed to 0.2 µM CsA for the initial 15 minutes (nonworking period) or the full 45-minute period of reperfusion. Coronary effluent was collected pre- and poststorage for assessment of lactate dehydrogenase release. Tissue samples were collected at the end of each study for immunoblotting and histological studies. RESULTS: CsA supplementation during cold storage or the first 15-minute reperfusion significantly improved functional recovery and significantly increased phospho-AMPKαThr172 and phospho-ULK-1Ser757. Hearts exposed to CsA for 45 minutes at reperfusion recovered poorly with no phospho-AMP-activated protein kinase α activation, decreased phospho-eNOSSer633, and decreased mitochondrial cytochrome c content with increased lactate dehydrogenase release. CONCLUSIONS: Inclusion of CsA during cold storage is cardioprotective. Effects of CsA addition to the perfusate during reperfusion were time dependent, with benefits at 15 minutes but not 45 minutes of reperfusion. The toxic effect with the presence of CsA for the full 45-minute reperfusion is associated with impaired mitochondrial integrity and decreased eNOS phosphorylation.

Functional recovery after dantrolene-supplementation of cold stored hearts using an ex vivo isolated working rat heart model.

The ryanodine receptor antagonist dantrolene inhibits calcium release from the sarcoplasmic reticulum and reduces cardiac ischaemia-reperfusion injury (IRI) in global warm ischaemia models however the cardioprotective potential of dantrolene under hypothermic conditions is unknown. This study addresses whether the addition of dantrolene during cardioplegia and hypothermic storage of the donor heart can improve functional recovery and reduce IRI. Using an ex vivo isolated working heart model, Wistar rat (3 month and 12 month) hearts were perfused to acquire baseline haemodynamic measurements of aortic flow, coronary flow, cardiac output, pulse pressure and heart rate. Hearts were arrested and stored in Celsior preservation solution supplemented with 0.2-40 µM dantrolene for 6 hours at 4°C, then reperfused (15 min Langendorff, 30 min working mode). In 3-month hearts, supplementation with 1 µM dantrolene significantly improved aortic flow and cardiac output compared to unsupplemented controls however lactate dehydrogenase (LDH) release and contraction bands were comparable. In contrast, 40 µM dantrolene-supplementation yielded poor cardiac recovery, increased post-reperfusion LDH but reduced contraction bands. All 3-month hearts stored in dantrolene displayed significantly reduced cleaved-caspase 3 intensities compared to controls. Analysis of cardioprotective signalling pathways showed no changes in AMPKα however dantrolene increased STAT3 and ERK1/2 signaling in a manner unrelated to functional recovery and AKT activity was reduced in 1 µM dantrolene-stored hearts. In contrast to 3-month hearts, no significant improvements were observed in the functional recovery of 12-month hearts following prolonged storage in 1 µM dantrolene. CONCLUSIONS: Dantrolene supplementation at 1 µM during hypothermic heart preservation improved functional recovery of young, but not older (12 month) hearts. Although the molecular mechanisms responsible for dantrolene-mediated cardioprotection are unclear, our studies show no correlation between improved functional recovery and SAFE and RISK pathway activation.

Normothermic ex-vivo preservation with the portable Organ Care System Lung device for bilateral lung transplantation (INSPIRE): a randomised, open-label, non-inferiority, phase 3 study.

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.

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.

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.