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J Card Surg. 2021 Jul;36(7):2592-2595. doi: 10.1111/jocs.15519. Epub 2021 Mar 30.

ABSTRACT

Cold storage preservation is the standard approach for heart transplantation but is a time-limited method of care. Ex vivo heart perfusion expands the donor pool due by mitigating time and distance barriers and allows the possibility to improve graft function. We report long term follow up of a successful heart transplantation following an ex vivo time of 17 h using the Organ Care System in a patient with a left ventricular assist device.

PMID:33783046 | DOI:10.1111/jocs.15519

Transplant Direct. 2021 May 18;7(6):e699. doi: 10.1097/TXD.0000000000001148. eCollection 2021 Jun.

ABSTRACT

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 ) 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.

PMID:34036169 | PMC:PMC8133134 | DOI:10.1097/TXD.0000000000001148

Interact Cardiovasc Thorac Surg. 2021 May 10;32(5):683-694. doi: 10.1093/icvts/ivaa333.

ABSTRACT

OBJECTIVES: The use of ‘extended criteria’ donor hearts and reconditioned hearts from donation after circulatory death has corresponded with an increase in primary graft dysfunction, with ischaemia-reperfusion injury being a major contributing factor in its pathogenesis. Limiting ischaemia-reperfusion injury through optimising donor heart preservation may significantly improve outcomes. We sought to review the literature to evaluate the evidence for this.

METHODS: A review of the published literature was performed to assess the potential impact of organ preservation optimisation on cardiac transplantation outcomes.

RESULTS: Ischaemia-reperfusion injury is a major factor in myocardial injury during transplantation with multiple potential therapeutic targets. Innate survival pathways have been identified, which can be mimicked with pharmacological conditioning. Although incompletely understood, discoveries in this domain have yielded extremely encouraging results with one of the most exciting prospects being the synergistic effect of selected agents. Ex situ heart perfusion is an additional promising adjunct.

CONCLUSIONS: Cardiac transplantation presents a unique opportunity to perfuse the whole heart before, or immediately after, the onset of ischaemia, thus maximising the potential for global cardioprotection while limiting possible systemic side effects. While clinical translation in the setting of myocardial infarction has often been disappointing, cardiac transplantation may afford the opportunity for cardioprotection to finally deliver on its preclinical promise.

PMID:33971665 | DOI:10.1093/icvts/ivaa333

Ann Palliat Med. 2021 Jun;10(6):7151-7152. doi: 10.21037/apm-2021-04. Epub 2021 May 18.

NO ABSTRACT

PMID:34044574 | DOI:10.21037/apm-2021-04

Transplant Direct. 2021 Feb 22;7(3):e676. doi: 10.1097/TXD.0000000000001120. eCollection 2021 Mar.

ABSTRACT

Organ donation after euthanasia is performed in an increasing number of countries. In this donation after circulatory death procedure, it has not been possible to donate the heart. Recent literature, however, reports positive results of heart donation after circulatory death. Therefore, patients who donate organs following euthanasia might be suitable candidates for heart donation. We want to confirm this assumption by sharing the results of 2 cases of heart donation following euthanasia with ex situ subnormothermic heart preservation. Our aim is to raise awareness of the potential of heart donation following euthanasia for both clinical transplantation and research.

METHODS: The data of 2 consecutive heart donations following euthanasia were collected prospectively. Informed consent was obtained from the patients themselves for heart donation for research purposes. An acellular oxygenated subnormothermic machine perfusion strategy was used to preserve both donor hearts. Subsequently, the hearts were evaluated on a normothermic perfusion machine using a balloon in the left ventricle.

RESULTS: Heart donation following euthanasia was feasible without significant changes in existing retrieval protocols. Duration of machine perfusion preservation was 408 and 432 minutes, for heart 1 and 2, respectively. For heart 1, developed pressure (P_dev) was 119 mm Hg, maximal rate of pressure rise (dP/dt_max), and fall (dP/dt_min) were 1524 mm Hg/s and -1057 mm Hg/s, respectively. For heart 2, P_dev was 142 mm Hg, dP/dt_max was 1098 mm Hg/s, and dP/dt_min was -802 mm Hg/s.

CONCLUSIONS: Hearts donated following euthanasia are highly valuable for research purposes and can have sufficient quality to be transplanted. With the implementation of ex situ heart perfusion, patients who are to donate their organs following euthanasia should also be able to donate their hearts. The complex combination of euthanasia and heart donation is ethically sound and surgically feasible and can contribute to shortening the heart transplant waiting list.

PMID:34104712 | PMC:PMC8183709 | DOI:10.1097/TXD.0000000000001120

Ann Thorac Surg. 2021 Jun 4:S0003-4975(21)00982-6. doi: 10.1016/j.athoracsur.2021.05.025. Online ahead of print.

ABSTRACT

BACKGROUND: Mortality for infants on the heart transplant wait list remains unacceptably high, and available mechanical circulatory support is suboptimal. Our goal is to demonstrate the feasibility of utilizing genetically engineered pig (GEP) heart as a bridge to allotransplantation by transplantation of a GEP heart in a baboon.

METHODS: Four baboons underwent orthotopic cardiac transplantation from GEP donors. All donor pigs had galactosyl-1,3-galactose knocked out. Two donor pigs had human complement regulatory CD55 transgene and the other 2 had human complement regulatory CD46 and thrombomodulin. Induction immunosuppression included thymoglobulin, and Anti-CD20. Maintenance immunosuppression was Rapamycin, AntiCD-40 and methylprednisolone. One donor heart was preserved with University of Wisconsin (UW) solution and the other three with del Nido solution.

RESULTS: All baboons weaned from cardiopulmonary bypass. B217 received a donor heart preserved with UW. Ventricular arrhythmias and depressed cardiac function resulted in early death. All recipients of del Nido preserved hearts easily weaned from cardiopulmonary bypass with minimal inotropic support. B15416 and B1917 survived for 90 days and 241 days respectively. Histopathology in B15416 revealed no significant myocardial rejection but cellular infiltrate around Purkinje fibers. Histopathology in B1917 was consistent with severe rejection. B37367 had uneventful transplant but developed significant respiratory distress with a cardiac arrest.

CONCLUSIONS: Survival of B15416 and B1917 demonstrates the feasibility of pursuing additional research to document the ability to bridge an infant to cardiac allotransplant with a GEP heart.

PMID:34097894 | DOI:10.1016/j.athoracsur.2021.05.025

JAMA Cardiol. 2021 Jun 23:e211825. doi: 10.1001/jamacardio.2021.1825. Online ahead of print.

ABSTRACT

IMPORTANCE: Coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) may contribute to the pathophysiologic characteristics of heart failure with preserved ejection fraction (HFpEF). However, the prevalence of CAD and CMD have not been systematically studied.

OBJECTIVE: To examine the prevalence of CAD and CMD in hospitalized patients with HFpEF.

DESIGN, SETTING, AND PARTICIPANTS: A total of 106 consecutive patients hospitalized with HFpEF were evaluated in this prospective, multicenter, cohort study conducted between January 2, 2017, and August 1, 2018; data analysis was performed from March 4 to September 6, 2019. Participants underwent coronary angiography with guidewire-based assessment of coronary flow reserve, index of microvascular resistance, and fractional flow reserve, followed by coronary vasoreactivity testing. Cardiac magnetic resonance imaging was performed with late gadolinium enhancement and assessment of extracellular volume. Myocardial perfusion was assessed qualitatively and semiquantitatively using the myocardial-perfusion reserve index.

MAIN OUTCOMES AND MEASURES: The prevalence of obstructive epicardial CAD, CMD, and myocardial ischemia, infarction, and fibrosis.

RESULTS: Of 106 participants enrolled (53 ).

CONCLUSIONS AND RELEVANCE: In this cohort study, 91% of patients with HFpEF had evidence of epicardial CAD, CMD, or both. Of those without obstructive CAD, 81% had CMD. Obstructive epicardial CAD and CMD appear to be common and often unrecognized in hospitalized patients with HFpEF and may be therapeutic targets.

PMID:34160566 | PMC:PMC8223134 | DOI:10.1001/jamacardio.2021.1825

J Card Surg. 2021 Sep;36(9):3421-3424. doi: 10.1111/jocs.15733. Epub 2021 Jun 12.

ABSTRACT

BACKGROUND: Heart transplantation from controlled donation after the circulatory determination of death (cDCDD) may be an option to increase the pool of grafts for transplantation.

MATERIALS AND METHODS: Initial experiences on cDCDD heart transplantation were based on the direct procurement of the heart followed by preservation with ex situ perfusion devices. Later, the use of thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as an option to recover hearts. We present a case of a heart transplant using a graft from controlled donation after circulatory death. Cardiac preservation was performed by postmortem TA-NRP followed by cold storage. Ex situ perfusion device was not used.

DISCUSSION AND CONCLUSION: This is one of the first published cases of a controlled donation after circulatory death heart retrieved using only TA-NRP and successfully transplanted.

PMID:34117800 | DOI:10.1111/jocs.15733

Front Immunol. 2021 Jun 9;12:667093. doi: 10.3389/fimmu.2021.667093. eCollection 2021.

ABSTRACT

BACKGROUND: Perioperative cardiac xenograft dysfunction (PCXD) describes a rapidly developing loss of cardiac function after xenotransplantation. PCXD occurs despite genetic modifications to increase compatibility of the heart. We report on the incidence of PCXD using static preservation in ice slush following crystalloid or blood-based cardioplegia versus continuous cold perfusion with XVIVO^© heart solution (XHS) based cardioplegia.

METHODS: Baboons were weight matched to genetically engineered swine heart donors. Cardioplegia volume was 30 cc/kg by donor weight, with del Nido cardioplegia and the addition of 25% by volume of donor whole blood. Continuous perfusion was performed using an XVIVO ^© Perfusion system with XHS to which baboon RBCs were added.

RESULTS: PCXD was observed in 5/8 that were preserved with crystalloid cardioplegia followed by traditional cold, static storage on ice. By comparison, when blood cardioplegia was used followed by cold, static storage, PCXD occurred in 1/3 hearts and only in 1/5 hearts that were induced with XHS blood cardioplegia followed by continuous perfusion. Survival averaged 17 hours in those with traditional preservation and storage, followed by 11.47 days and 15.03 days using blood cardioplegia and XHS+continuous preservation, respectively. Traditional preservation resulted in more inotropic support and higher average peak serum lactate 14.3±1.7 mmol/L compared to blood cardioplegia 3.6±3.0 mmol/L and continuous perfusion 3.5±1.5 mmol/L.

CONCLUSION: Blood cardioplegia induction, alone or followed by XHS perfusion storage, reduced the incidence of PCXD and improved graft function and survival, relative to traditional crystalloid cardioplegia-slush storage alone.

PMID:34177906 | PMC:PMC8220198 | DOI:10.3389/fimmu.2021.667093

World J Transplant. 2021 Jun 18;11(6):203-211. doi: 10.5500/wjt.v11.i6.203.

ABSTRACT

Hyperkalemia is a recognized and potentially life-threatening complication of heart transplantation. In the complex biosystem created by transplantation, recipients are susceptible to multiple mechanisms for hyperkalemia which are discussed in detail in this manuscript. Hyperkalemia in heart transplantation could occur pre-transplant, during the transplant period, or post-transplant. Pre-transplant causes of hyperkalemia include hypothermia, donor heart preservation solutions, conventional cardioplegia, normokalemic cardioplegia, continuous warm reperfusion technique, and ex-vivo heart perfusion. Intra-transplant causes of hyperkalemia include anesthetic medications used during the procedure, heparinization, blood transfusions, and a low output state. Finally, post-transplant causes of hyperkalemia include hemostasis and drug-induced hyperkalemia. Hyperkalemia has been studied in kidney and liver transplant recipients, but there is limited data on the incidence, causes, management, and prevention in heart transplant recipients. Hyperkalemia is associated with an increased risk of hospital mortality and readmission in these patients. This review describes the current literature pertaining to the causes, pathophysiology, and treatment of hyperkalemia in patients undergoing heart transplantation and focuses primarily on post-heart transplantation.

PMID:34164295 | PMC:PMC8218349 | DOI:10.5500/wjt.v11.i6.203